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Selective Immunoglobulin A Deficiency
Yoavanit Srivaro M.D.
Outlines
•Introduction
•Immunoglobulin A and Its Functions
•Pathogenesis
•Epidemiology
•Clinical Manifestations
•Laboratory Evaluation
•Management
•Prognosis
Introduction
Benjasupattananan P, Simasathein T, Vichyanond P, Leungwedchakarn V, Visitsunthorn N, Pacharn P, et al. Clinical characteristics and outcomes of
primary immunodeficiencies in Thai children: an 18-year experience from a tertiary care center. Journal of clinical immunology. 2009;29:357-64.
Benjasupattananan P, Simasathein T, Vichyanond P, Leungwedchakarn V, Visitsunthorn N, Pacharn P, et al. Clinical characteristics and outcomes of
primary immunodeficiencies in Thai children: an 18-year experience from a tertiary care center. Journal of clinical immunology. 2009;29:357-64.
Predominantly antibody deficiency
Recurrent bacterial infection :Otitis,Pneumonia,Sinusitis,Diarrhea,Sepsis
Bousfiha AA, Jeddane L, Ailal F, Al Herz W, Conley ME, Cunningham-Rundles C, et al. A phenotypic approach for IUIS PID classification and diagnosis: guidelines for clinicians at the bedside. Journal of clinical immunology. 2013;33:1078-87.
Predominantly antibody deficiency
Recurrent bacterial infection :Otitis,Pneumonia,Sinusitis,Diarrhea,Sepsis
Bousfiha AA, Jeddane L, Ailal F, Al Herz W, Conley ME, Cunningham-Rundles C, et al. A phenotypic approach for IUIS PID classification and diagnosis: guidelines for clinicians at the bedside. Journal of clinical immunology. 2013;33:1078-87.
Serum Immunoglobulin Assay : IgG,IgA,IgM
Predominantly antibody deficiency
Recurrent bacterial infection :Otitis,Pneumonia,Sinusitis,Diarrhea,Sepsis
Bousfiha AA, Jeddane L, Ailal F, Al Herz W, Conley ME, Cunningham-Rundles C, et al. A phenotypic approach for IUIS PID classification and diagnosis: guidelines for clinicians at the bedside. Journal of clinical immunology. 2013;33:1078-87.
Serum Immunoglobulin Assay : IgG,IgA,IgM
IgG,IgA and/or IgM
Predominantly antibody deficiency
Recurrent bacterial infection :Otitis,Pneumonia,Sinusitis,Diarrhea,Sepsis
Bousfiha AA, Jeddane L, Ailal F, Al Herz W, Conley ME, Cunningham-Rundles C, et al. A phenotypic approach for IUIS PID classification and diagnosis: guidelines for clinicians at the bedside. Journal of clinical immunology. 2013;33:1078-87.
Serum Immunoglobulin Assay : IgG,IgA,IgM
IgG,IgA and/or IgM
B lymphocyte CD 19+
Predominantly antibody deficiency
Recurrent bacterial infection :Otitis,Pneumonia,Sinusitis,Diarrhea,Sepsis
Bousfiha AA, Jeddane L, Ailal F, Al Herz W, Conley ME, Cunningham-Rundles C, et al. A phenotypic approach for IUIS PID classification and diagnosis: guidelines for clinicians at the bedside. Journal of clinical immunology. 2013;33:1078-87.
Serum Immunoglobulin Assay : IgG,IgA,IgM
IgG,IgA and/or IgM
B lymphocyte CD 19+
CD 19+ absent
X-Linked Agammaglobulinemia
Predominantly antibody deficiency
Recurrent bacterial infection :Otitis,Pneumonia,Sinusitis,Diarrhea,Sepsis
Bousfiha AA, Jeddane L, Ailal F, Al Herz W, Conley ME, Cunningham-Rundles C, et al. A phenotypic approach for IUIS PID classification and diagnosis: guidelines for clinicians at the bedside. Journal of clinical immunology. 2013;33:1078-87.
Serum Immunoglobulin Assay : IgG,IgA,IgM
IgG,IgA and/or IgM
B lymphocyte CD 19+
CD 19+ absent
X-Linked Agammaglobulinemia
CD 19+ >1%
CVID
Predominantly antibody deficiency
Recurrent bacterial infection :Otitis,Pneumonia,Sinusitis,Diarrhea,Sepsis
Bousfiha AA, Jeddane L, Ailal F, Al Herz W, Conley ME, Cunningham-Rundles C, et al. A phenotypic approach for IUIS PID classification and diagnosis: guidelines for clinicians at the bedside. Journal of clinical immunology. 2013;33:1078-87.
Serum Immunoglobulin Assay : IgG,IgA,IgM
IgG,IgA and/or IgM
B lymphocyte CD 19+
CD 19+ absent
X-Linked Agammaglobulinemia
CD 19+ >1%
CVID
IgG and IgA and normal or IgM
Predominantly antibody deficiency
Recurrent bacterial infection :Otitis,Pneumonia,Sinusitis,Diarrhea,Sepsis
Bousfiha AA, Jeddane L, Ailal F, Al Herz W, Conley ME, Cunningham-Rundles C, et al. A phenotypic approach for IUIS PID classification and diagnosis: guidelines for clinicians at the bedside. Journal of clinical immunology. 2013;33:1078-87.
Serum Immunoglobulin Assay : IgG,IgA,IgM
IgG,IgA and/or IgM
B lymphocyte CD 19+
CD 19+ absent
X-Linked Agammaglobulinemia
CD 19+ >1%
CVID
IgG and IgA and normal or IgM
Transient hypogammaglo-bulinemia of
infancy
Predominantly antibody deficiency
Recurrent bacterial infection :Otitis,Pneumonia,Sinusitis,Diarrhea,Sepsis
Bousfiha AA, Jeddane L, Ailal F, Al Herz W, Conley ME, Cunningham-Rundles C, et al. A phenotypic approach for IUIS PID classification and diagnosis: guidelines for clinicians at the bedside. Journal of clinical immunology. 2013;33:1078-87.
Serum Immunoglobulin Assay : IgG,IgA,IgM
IgG,IgA and/or IgM
B lymphocyte CD 19+
CD 19+ absent
X-Linked Agammaglobulinemia
CD 19+ >1%
CVID
IgG and IgA and normal or IgM
Transient hypogammaglo-bulinemia of
infancy
Predominantly antibody deficiency
Recurrent bacterial infection :Otitis,Pneumonia,Sinusitis,Diarrhea,Sepsis
Bousfiha AA, Jeddane L, Ailal F, Al Herz W, Conley ME, Cunningham-Rundles C, et al. A phenotypic approach for IUIS PID classification and diagnosis: guidelines for clinicians at the bedside. Journal of clinical immunology. 2013;33:1078-87.
Serum Immunoglobulin Assay : IgG,IgA,IgM
IgG,IgA and/or IgM
B lymphocyte CD 19+
CD 19+ absent
X-Linked Agammaglobulinemia
CD 19+ >1%
CVID
IgG and IgA and normal or IgM
Transient hypogammaglo-bulinemia of
infancy
HyperIgMsyndrome
Predominantly antibody deficiency
Recurrent bacterial infection :Otitis,Pneumonia,Sinusitis,Diarrhea,Sepsis
Serum Immunoglobulin Assay : IgG,IgA,IgM
IgG,IgA and/or IgMIgG and IgA and normal or IgM
Normal IgG,IgA,IgM
B lymphocyte CD 19+
CD 19+ absent CD 19+ >1%
X-Linked Agammaglobulinemia
CVIDHyperIgMsyndrome
Transient hypogammaglo-bulinemia of
infancy
Bousfiha AA, Jeddane L, Ailal F, Al Herz W, Conley ME, Cunningham-Rundles C, et al. A phenotypic approach for IUIS PID classification and diagnosis: guidelines for clinicians at the bedside. Journal of clinical immunology. 2013;33:1078-87.
Predominantly antibody deficiency
Recurrent bacterial infection :Otitis,Pneumonia,Sinusitis,Diarrhea,Sepsis
Serum Immunoglobulin Assay : IgG,IgA,IgM
IgG,IgA and/or IgMIgG and IgA and normal or IgM
Normal IgG,IgA,IgM
B lymphocyte CD 19+
CD 19+ absent CD 19+ >1%
X-Linked Agammaglobulinemia
CVIDHyperIgMsyndrome
Transient hypogammaglo-bulinemia of
infancy
Bousfiha AA, Jeddane L, Ailal F, Al Herz W, Conley ME, Cunningham-Rundles C, et al. A phenotypic approach for IUIS PID classification and diagnosis: guidelines for clinicians at the bedside. Journal of clinical immunology. 2013;33:1078-87.
Abn Specific Ab resonseto vaccine
Specific Ab def.
Predominantly antibody deficiency
Recurrent bacterial infection :Otitis,Pneumonia,Sinusitis,Diarrhea,Sepsis
Bousfiha AA, Jeddane L, Ailal F, Al Herz W, Conley ME, Cunningham-Rundles C, et al. A phenotypic approach for IUIS PID classification and diagnosis: guidelines for clinicians at the bedside. Journal of clinical immunology. 2013;33:1078-87.
Serum Immunoglobulin Assay : IgG,IgA,IgM
IgG,IgA and/or IgM
B lymphocyte CD 19+
CD 19+ absent
X-Linked Agammaglobulinemia
CD 19+ >1%
CVID
IgG and IgA and normal or IgM
Transient hypogammaglo-bulinemia of
infancy
HyperIgMsyndrome
IgA Normal IgG,IgA,IgM
Abn Specific Ab resonseto vaccine
Specific Ab def.
Predominantly antibody deficiency
Recurrent bacterial infection :Otitis,Pneumonia,Sinusitis,Diarrhea,Sepsis
Serum Immunoglobulin Assay : IgG,IgA,IgM
IgG,IgA and/or IgMIgG and IgA and normal or IgM
IgA Normal IgG,IgA,IgM
B lymphocyte CD 19+
CD 19+ absent CD 19+ >1%
X-Linked Agammaglobulinemia
CVIDHyperIgMsyndrome
Transient hypogammaglo-bulinemia of
infancy
Specific Ab resonse to
vaccine
Abn Specific Ab resonseto vaccine
Specific Ab def.
Bousfiha AA, Jeddane L, Ailal F, Al Herz W, Conley ME, Cunningham-Rundles C, et al. A phenotypic approach for IUIS PID classification and diagnosis: guidelines for clinicians at the bedside. Journal of clinical immunology. 2013;33:1078-87.
Predominantly antibody deficiency
Recurrent bacterial infection :Otitis,Pneumonia,Sinusitis,Diarrhea,Sepsis
Serum Immunoglobulin Assay : IgG,IgA,IgM
IgG,IgA and/or IgMIgG and IgA and normal or IgM
IgA Normal IgG,IgA,IgM
B lymphocyte CD 19+
CD 19+ absent CD 19+ >1%
X-Linked Agammaglobulinemia
CVIDHyperIgMsyndrome
Transient hypogammaglo-bulinemia of
infancy
Specific Ab resonse to
vaccine
Abn Specific Ab resonseto vaccine
Specific Ab def.
Low
Bousfiha AA, Jeddane L, Ailal F, Al Herz W, Conley ME, Cunningham-Rundles C, et al. A phenotypic approach for IUIS PID classification and diagnosis: guidelines for clinicians at the bedside. Journal of clinical immunology. 2013;33:1078-87.
Predominantly antibody deficiency
Recurrent bacterial infection :Otitis,Pneumonia,Sinusitis,Diarrhea,Sepsis
Serum Immunoglobulin Assay : IgG,IgA,IgM
IgG,IgA and/or IgMIgG and IgA and normal or IgM
IgA Normal IgG,IgA,IgM
B lymphocyte CD 19+
CD 19+ absent CD 19+ >1%
X-Linked Agammaglobulinemia
CVIDHyperIgMsyndrome
Transient hypogammaglo-bulinemia of
infancy
Specific Ab resonse to
vaccine
IgA with Specific Ab def.
Abn Specific Ab resonseto vaccine
Specific Ab def.
Low
Bousfiha AA, Jeddane L, Ailal F, Al Herz W, Conley ME, Cunningham-Rundles C, et al. A phenotypic approach for IUIS PID classification and diagnosis: guidelines for clinicians at the bedside. Journal of clinical immunology. 2013;33:1078-87.
Predominantly antibody deficiency
Recurrent bacterial infection :Otitis,Pneumonia,Sinusitis,Diarrhea,Sepsis
Serum Immunoglobulin Assay : IgG,IgA,IgM
IgG,IgA and/or IgMIgG and IgA and normal or IgM
IgA Normal IgG,IgA,IgM
B lymphocyte CD 19+
CD 19+ absent CD 19+ >1%
X-Linked Agammaglobulinemia
CVIDHyperIgMsyndrome
Transient hypogammaglo-bulinemia of
infancy
Specific Ab resonse to
vaccine
Selective IgA def.
IgA with Specific Ab def.
Abn Specific Ab resonseto vaccine
Specific Ab def.
Normal Low
Bousfiha AA, Jeddane L, Ailal F, Al Herz W, Conley ME, Cunningham-Rundles C, et al. A phenotypic approach for IUIS PID classification and diagnosis: guidelines for clinicians at the bedside. Journal of clinical immunology. 2013;33:1078-87.
Selective IgA Deficiency
“First described in 1964”
Rockey JH, Hanson LA, Heremans JF, Kunkel HG. BETA-2A AGLOBULINEMIA IN TWO HEALTHY MEN. The Journal of laboratory and clinical medicine. 1964;63:205-12.
Rockey JH, Hanson LA, Heremans JF, Kunkel HG. BETA-2A AGLOBULINEMIA IN TWO HEALTHY MEN. The Journal of laboratory and clinical medicine. 1964;63:205-12.
Definition
•Male or female greater than 4 years of age
•Serum IgA of less than 7 mg/dL (0.07 g/L)
•Normal serum IgG and IgM
•Other causes of hypogammaglobulinemia have
been excluded
•Normal IgG antibody response to vaccination
Conley ME, Notarangelo LD, Etzioni A. Diagnostic criteria for primary immunodeficiencies. Representing PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies). Clinical immunology (Orlando, Fla). 1999;93:190-7.
Ballas ZK, Chinen J, Frank MM, Hsu JT, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. The Journal of allergy and clinical immunology. 2015.
Definition
•Male or female greater than 4 years of age
•Serum IgA of less than 7 mg/dL (0.07 g/L)
•Normal serum IgG and IgM
•Other causes of hypogammaglobulinemia have
been excluded
•Normal IgG antibody response to vaccinationBallas ZK, Chinen J, Frank MM, Hsu JT, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. The Journal of
allergy and clinical immunology. 2015.
Conley ME, Notarangelo LD, Etzioni A. Diagnostic criteria for primary immunodeficiencies. Representing PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies). Clinical immunology (Orlando, Fla). 1999;93:190-7.
Definition
•Male or female greater than 4 years of age
•Serum IgA of less than 7 mg/dL (0.07 g/L)
•Normal serum IgG and IgM
•Other causes of hypogammaglobulinemia have
been excluded
•Normal IgG antibody response to vaccinationBallas ZK, Chinen J, Frank MM, Hsu JT, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. The Journal of
allergy and clinical immunology. 2015.
Conley ME, Notarangelo LD, Etzioni A. Diagnostic criteria for primary immunodeficiencies. Representing PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies). Clinical immunology (Orlando, Fla). 1999;93:190-7.
Definition
•Male or female greater than 4 years of age
•Serum IgA of less than 7 mg/dL (0.07 g/L)
•Normal serum IgG and IgM
•Other causes of hypogammaglobulinemia have
been excluded
•Normal IgG antibody response to vaccinationBallas ZK, Chinen J, Frank MM, Hsu JT, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. The Journal of
allergy and clinical immunology. 2015.
Conley ME, Notarangelo LD, Etzioni A. Diagnostic criteria for primary immunodeficiencies. Representing PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies). Clinical immunology (Orlando, Fla). 1999;93:190-7.
Definition
•Male or female greater than 4 years of age
•Serum IgA of less than 7 mg/dL (0.07 g/L)
•Normal serum IgG and IgM
•Other causes of hypogammaglobulinemia have
been excluded
•Normal IgG antibody response to vaccination
Conley ME, Notarangelo LD, Etzioni A. Diagnostic criteria for primary immunodeficiencies. Representing PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies). Clinical immunology (Orlando, Fla). 1999;93:190-7.
Ballas ZK, Chinen J, Frank MM, Hsu JT, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. The Journal of allergy and clinical immunology. 2015.
Partial Ig A Deficiency
•Male or female greater than 4 years of age
•Serum IgA at least 2 SD below normal for age
•Normal serum IgG and IgM
Conley ME, Notarangelo LD, Etzioni A. Diagnostic criteria for primary immunodeficiencies. Representing PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies).
Clinical immunology (Orlando, Fla). 1999;93:190-7.
Immunoglobulin A And Its Functions
Immunoglobulin A
“First described in serum in 1953”
Grabar P, Williams CA. [Method permitting the combined study of the electrophoretic and the immunochemical properties of protein mixtures; application to blood serum]. Biochimica et biophysica acta.
1953;10:193-4.
Distribution
•Most abundant antibody isotypes
•60-70% of total production of antibodies
•Majority of IgA
1.Mucous secretion
:Saliva,Milk,Colostrum,Tears
2.Secretion from
:Respiratory tract ,Genitourinary tract ,Prostate
Abbas AK, Lichtman AH, Pillai S. Cellular and molecular immunology. 8th ed.Philadelphia, W.B. Saunders Company.2015.
Woof JM, Kerr MA. The function of immunoglobulin A in immunity. The Journal of pathology.2006;208(2):270-82.
Normal Serum Level
• IgA is the second most abundant isotype in the circulation.
•Range from 61 to 356 mg/dL.
Woof JM, Kerr MA. The function of immunoglobulin A in immunity. The Journal of pathology.2006;208(2):270-82.
Jolliff CR, Cost KM, Stivrins PC, Grossman PP, Nolte CR, Franco SM, et al. Reference intervals for serum IgG,
IgA, IgM, C3, and C4 as determined by rate nephelometry. Clinical chemistry. 1982;28:126-8.
Figure 3-7 Basic structure of immunoglobulin molecules.
Jelinek DF,Li JT.Immunoglobulin Structure and Function In: Adkinson NF,Bochner BS, Burks AW,Busse WW,Holgate ST, Lemanske RF, O’Hehir RE, editors. Middleton’s allergy: principles & practice. 8 th ed.
Philadelphia: Mosby-Elsevier; 2014. p.30-44.
Figure 3-7 Basic structure of immunoglobulin molecules.
Jelinek DF,Li JT.Immunoglobulin Structure and Function In: Adkinson NF,Bochner BS, Burks AW,Busse WW,Holgate ST, Lemanske RF, O’Hehir RE, editors. Middleton’s allergy: principles & practice. 8 th ed.
Philadelphia: Mosby-Elsevier; 2014. p.30-44.
Figure 3-7 Basic structure of immunoglobulin molecules.
Jelinek DF,Li JT.Immunoglobulin Structure and Function In: Adkinson NF,Bochner BS, Burks AW,Busse WW,Holgate ST, Lemanske RF, O’Hehir RE, editors. Middleton’s allergy: principles & practice. 8 th ed.
Philadelphia: Mosby-Elsevier; 2014. p.30-44.
Figure 1. Human IgA structure.
Woof JM, Russell MW. Structure and function relationships in IgA. Mucosal immunology. 2011;4:590-7.
Woof JM, Russell MW. Structure and function relationships in IgA. Mucosal immunology. 2011;4:590-7.
Figure 1. Human IgA structure.
Woof JM, Russell MW. Structure and function relationships in IgA. Mucosal immunology. 2011;4:590-7.
Figure 1. Human IgA structure.
Figure 3-7 Basic structure of immunoglobulin molecules.
Jelinek DF,Li JT.Immunoglobulin Structure and Function In: Adkinson NF,Bochner BS, Burks AW,Busse WW,Holgate ST, Lemanske RF, O’Hehir RE, editors. Middleton’s allergy: principles & practice. 8 th ed.
Philadelphia: Mosby-Elsevier; 2014. p.30-44.
Monomeric Serum IgA
Dimeric form IgA
Woof JM, Russell MW. Structure and function relationships in IgA. Mucosal immunology. 2011;4:590-7.
Figure 1. Human IgA structure.
Dimeric form IgA
Woof JM, Russell MW. Structure and function relationships in IgA. Mucosal immunology. 2011;4:590-7.
Figure 1. Human IgA structure.
Figure 3-7 Basic structure of immunoglobulin molecules.
Jelinek DF,Li JT.Immunoglobulin Structure and Function In: Adkinson NF,Bochner BS, Burks AW,Busse WW,Holgate ST, Lemanske RF, O’Hehir RE, editors. Middleton’s allergy: principles & practice. 8 th ed.
Philadelphia: Mosby-Elsevier; 2014. p.30-44.
Dimeric form IgA
Figure 3-7 Basic structure of immunoglobulin molecules.
Jelinek DF,Li JT.Immunoglobulin Structure and Function In: Adkinson NF,Bochner BS, Burks AW,Busse WW,Holgate ST, Lemanske RF, O’Hehir RE, editors. Middleton’s allergy: principles & practice. 8 th ed.
Philadelphia: Mosby-Elsevier; 2014. p.30-44.
Dimeric form IgA
Production
From Plasma cell in Bone marrow
From Locally in the mucosal tissue
Woof JM, Kerr MA. The function of immunoglobulin A in immunity. The Journal of pathology. 2006;208:270-82.
Serum IgA
Abbas AK, Lichtman AH, Pillai S. Cellular and molecular immunology. 8th ed.Philadelphia, W.B. Saunders Company.2015.Jelinek DF,Li JT.Immunoglobulin Structure and Function In: Adkinson NF,Bochner BS,Burks AW,Busse WW,Holgate ST,
Lemanske RF, O’Hehir RE, editors. Middleton’s allergy: principles & practice. 8 th ed. Philadelphia: Mosby-Elsevier; 2014. p.30-44.
Figure 3-8 Germline organization of human immunoglobulin gene loci.
Abbas AK, Lichtman AH, Pillai S. Cellular and molecular immunology. 8th ed.Philadelphia, W.B. Saunders Company.2015.Jelinek DF,Li JT.Immunoglobulin Structure and Function In: Adkinson NF,Bochner BS,Burks AW,Busse WW,Holgate ST,
Lemanske RF, O’Hehir RE, editors. Middleton’s allergy: principles & practice. 8 th ed. Philadelphia: Mosby-Elsevier; 2014. p.30-44.
Figure 3-8 Germline organization of human immunoglobulin gene loci.
Abbas AK, Lichtman AH, Pillai S. Cellular and molecular immunology. 8th ed.Philadelphia, W.B. Saunders Company.2015.
FIGURE 14-7 A IgA class switching in the gut. T-dependent IgA class switching
Abbas AK, Lichtman AH, Pillai S. Cellular and molecular immunology. 8th ed.Philadelphia, W.B. Saunders Company.2015.
FIGURE 14-7 A IgA class switching in the gut. T-dependent IgA class switching
Abbas AK, Lichtman AH, Pillai S. Cellular and molecular immunology. 8th ed.Philadelphia, W.B. Saunders Company.2015.
FIGURE 14-7 A IgA class switching in the gut. T-dependent IgA class switching
Abbas AK, Lichtman AH, Pillai S. Cellular and molecular immunology. 8th ed.Philadelphia, W.B. Saunders Company.2015.
FIGURE 14-7 A IgA class switching in the gut. T-dependent IgA class switching
Abbas AK, Lichtman AH, Pillai S. Cellular and molecular immunology. 8th ed.Philadelphia, W.B. Saunders Company.2015.
FIGURE 14-7 A IgA class switching in the gut. T-dependent IgA class switching
Abbas AK, Lichtman AH, Pillai S. Cellular and molecular immunology. 8th ed.Philadelphia, W.B. Saunders Company.2015.
FIGURE 14-7 A IgA class switching in the gut. T-dependent IgA class switching
Abbas AK, Lichtman AH, Pillai S. Cellular and molecular immunology. 8th ed.Philadelphia, W.B. Saunders Company.2015.
FIGURE 14-7 A IgA class switching in the gut. T-dependent IgA class switching
Abbas AK, Lichtman AH, Pillai S. Cellular and molecular immunology. 8th ed.Philadelphia, W.B. Saunders Company.2015.
FIGURE 14-7 A IgA class switching in the gut. T-dependent IgA class switching
Abbas AK, Lichtman AH, Pillai S. Cellular and molecular immunology. 8th ed.Philadelphia, W.B. Saunders Company.2015.
FIGURE 14-7 A IgA class switching in the gut. T-dependent IgA class switching
Abbas AK, Lichtman AH, Pillai S. Cellular and molecular immunology. 8th ed.Philadelphia, W.B. Saunders Company.2015.
FIGURE 14-7 B IgA class switching in the gut. T-independent IgA class switching
Abbas AK, Lichtman AH, Pillai S. Cellular and molecular immunology. 8th ed.Philadelphia, W.B. Saunders Company.2015.
FIGURE 14-7 B IgA class switching in the gut. T-independent IgA class switching
Abbas AK, Lichtman AH, Pillai S. Cellular and molecular immunology. 8th ed.Philadelphia, W.B. Saunders Company.2015.
FIGURE 14-7 B IgA class switching in the gut. T-independent IgA class switching
Abbas AK, Lichtman AH, Pillai S. Cellular and molecular immunology. 8th ed.Philadelphia, W.B. Saunders Company.2015.
FIGURE 14-7 B IgA class switching in the gut. T-independent IgA class switching
Abbas AK, Lichtman AH, Pillai S. Cellular and molecular immunology. 8th ed.Philadelphia, W.B. Saunders Company.2015.
FIGURE 14-7 B IgA class switching in the gut. T-independent IgA class switching
Abbas AK, Lichtman AH, Pillai S. Cellular and molecular immunology. 8th ed.Philadelphia, W.B. Saunders Company.2015.
FIGURE 14-8 Transport of IgA across epithelial cells.
Abbas AK, Lichtman AH, Pillai S. Cellular and molecular immunology. 8th ed.Philadelphia, W.B. Saunders Company.2015.
FIGURE 14-8 Transport of IgA across epithelial cells.
Abbas AK, Lichtman AH, Pillai S. Cellular and molecular immunology. 8th ed.Philadelphia, W.B. Saunders Company.2015.
FIGURE 14-8 Transport of IgA across epithelial cells.
Abbas AK, Lichtman AH, Pillai S. Cellular and molecular immunology. 8th ed.Philadelphia, W.B. Saunders Company.2015.
FIGURE 14-8 Transport of IgA across epithelial cells.
Abbas AK, Lichtman AH, Pillai S. Cellular and molecular immunology. 8th ed.Philadelphia, W.B. Saunders Company.2015.
FIGURE 14-8 Transport of IgA across epithelial cells.
Abbas AK, Lichtman AH, Pillai S. Cellular and molecular immunology. 8th ed.Philadelphia, W.B. Saunders Company.2015.
FIGURE 14-8 Transport of IgA across epithelial cells.
FIGURE 3-11 Fc receptor expression pattern on human cells and biologic activity.
Jelinek DF,Li JT.Immunoglobulin Structure and Function In: Adkinson NF,Bochner BS, Burks AW,Busse WW,Holgate ST, Lemanske RF, O’Hehir RE, editors. Middleton’s allergy: principles & practice. 8 th ed. Philadelphia: Mosby-Elsevier; 2014. p.30-44.
Fig. 1 a Schematic representation of immunoglobulin A (IgA) binding to the Fc alpha RI–FcR gammachain
Mkaddem SB, Christou I, Rossato E, Berthelot L, Lehuen A, Monteiro RC.In IgA, IgA receptors, and their anti-inflammatory properties In : Daëron M, Nimmerjahn F,editors :Current Topics in Microbiology and
Immunology . 1st ed. Switzerland Springer International Publishing; 2014. p221-35 .
Fig. 2 Simplified scheme of Fc alpha RI signaling pathways
Mkaddem SB, Christou I, Rossato E, Berthelot L, Lehuen A, Monteiro RC.In IgA, IgA receptors, and their anti-inflammatory properties In : Daëron M, Nimmerjahn F,editors :Current Topics in Microbiology and
Immunology . 1st ed. Switzerland Springer International Publishing; 2014. p221-35 .
Activation
Mkaddem SB, Christou I, Rossato E, Berthelot L, Lehuen A, Monteiro RC.In IgA, IgA receptors, and their anti-inflammatory properties In : Daëron M, Nimmerjahn F,editors :Current Topics in Microbiology and
Immunology . 1st ed. Switzerland Springer International Publishing; 2014. p221-35 .
Inhibition
Fig. 1 a Schematic representation of immunoglobulin A (IgA) binding to the Fc alpha RI–FcRc-chain
Fig. 1 b DC-SIGN/SIGNR1 and secretory IgA (SIgA) representation
Mkaddem SB, Christou I, Rossato E, Berthelot L, Lehuen A, Monteiro RC.In IgA, IgA receptors, and their anti-inflammatory properties In : Daëron M, Nimmerjahn F,editors :Current Topics in Microbiology and
Immunology . 1st ed. Switzerland Springer International Publishing; 2014. p221-35 .
Regulatory Function
Jelinek DF,Li JT.Immunoglobulin Structure and Function In: Adkinson NF,Bochner BS, Burks AW,Busse WW,Holgate ST, Lemanske RF, O’Hehir RE, editors. Middleton’s allergy: principles & practice. 8 th ed.
Philadelphia: Mosby-Elsevier; 2014. p.30-44.
Jelinek DF,Li JT.Immunoglobulin Structure and Function In: Adkinson NF,Bochner BS, Burks AW,Busse WW,Holgate ST, Lemanske RF, O’Hehir RE, editors. Middleton’s allergy: principles & practice. 8 th ed.
Philadelphia: Mosby-Elsevier; 2014. p.30-44.
Jelinek DF,Li JT.Immunoglobulin Structure and Function In: Adkinson NF,Bochner BS, Burks AW,Busse WW,Holgate ST, Lemanske RF, O’Hehir RE, editors. Middleton’s allergy: principles & practice. 8 th ed.
Philadelphia: Mosby-Elsevier; 2014. p.30-44.
Pathogenesis
Stem Cells Defect
Yel L. Selective IgA deficiency. Journal of clinical immunology. 2010;30:10-6.
Hammarstrom L, Lonnqvist B, Ringden O, Smith CI, Wiebe T. Transfer of IgA deficiency to a bone-marrow-grafted patient with aplastic anaemia. Lancet (London, England). 1985;1:778-81.
Hammarstrom L, Lonnqvist B, Ringden O, Smith CI, Wiebe T. Transfer of IgA deficiency to a bone-marrow-grafted patient with aplastic anaemia. Lancet (London, England). 1985;1:778-81.
Block in differentiation of B cells to IgA antibody secreting plasma cell
Abbas AK, Lichtman AH, Pillai S. Cellular and molecular immunology. 8th ed.Philadelphia, W.B. Saunders Company.2015.
FIG. 1. Overview of B-cell development and defects causing antibody deficiency.
Fried AJ, Bonilla FA. Pathogenesis, diagnosis, and management of primary antibody deficiencies and infections. Clinical microbiology reviews. 2009;22:396-414.
Nechvatalova J, Pikulova Z, Stikarovska D, Pesak S, Vlkova M, Litzman J. B-lymphocyte subpopulations in patients with selective IgA deficiency. Journal of clinical immunology. 2012;32(3):441-8.
Alpha heavy chain gene deletionsinvolving various segments on chromosome 14
Suzuki H, Kaneko H, Fukao T, Jin R, Kawamoto N, Asano T, et al. Various expression patterns of alpha1 and alpha2 genes in IgA deficiency. Allergology international : official journal of the Japanese Society of
Allergology. 2009;58:111-7.
Suzuki H, Kaneko H, Fukao T, Jin R, Kawamoto N, Asano T, et al. Various expression patterns of alpha1 and alpha2 genes in IgA deficiency. Allergology international : official journal of the Japanese Society of
Allergology. 2009;58:111-7.
TACI and BAFFR gene Abnormality
Rachid R, Castigli E, Geha RS, Bonilla FA. TACI mutation in common variable immunodeficiency and IgA deficiency. Current allergy and asthma reports. 2006;6:357-62.
Abnormality of The Cytokine network
Cunningham-Rundles C. Physiology of IgA and IgA deficiency. JClin Immunol. 2001;21:303–9.
• IL-4
• IL-6
• IL-7
• IL-10
• TGF-β
• IL-21
Cunningham-Rundles C. Physiology of IgA and IgA deficiency. JClin Immunol. 2001;21:303–9.
Genetic
MHC loci associations
The 8.1 Haplotype
MHC Haplotype A1,B8,DR3,DQ2
Wikipedia. HLA A1-B8-DR3-DQ2 [Internet]. 2015 [cited 2015 Sep 19]. Available from:http://en.wikipedia.org/wiki/HLA A1-B8-DR3-DQ2
The 8.1 Haplotype
MHC Haplotype A1,B8,DR3,DQ2
IgA deficiency Patients Healthy polpulation
45% 16%
Singh K, Chang C, Gershwin ME. IgA deficiency and autoimmunity. Autoimmunity reviews. 2014;13:163-77.
Mohammadi J, Ramanujam R, Jarefors S, Rezaei N, Aghamohammadi A, Gregersen PK, et al. IgA deficiency and the MHC: assessment of relative risk and microheterogeneity within the HLA A1 B8, DR3 (8.1)
haplotype. Journal of clinical immunology. 2010;30:138-43.
Abnormalities in genes associated with autoimmunity
IF1H1 =Interferon induced with helicase C domain 1 protein
Ferreira RC, Pan-Hammarstrom Q, Graham RR, Gateva V, Fontan G, Lee AT, et al. Association of IFIH1 and other autoimmunity risk alleles with selective IgA deficiency. Nature genetics. 2010;42(9):777-80.
Wang N, Shen N, Vyse TJ, Anand V, Gunnarson I, Sturfelt G, et al. Selective IgA deficiency in autoimmune diseases. Molecular medicine (Cambridge, Mass). 2011;17(11-12):1383-96.
CLEC 16 A =C-type lectin domain family 16
Ferreira RC, Pan-Hammarstrom Q, Graham RR, Gateva V, Fontan G, Lee AT, et al. Association of IFIH1 and other autoimmunity risk alleles with selective IgA deficiency. Nature genetics. 2010;42(9):777-80.
Wang N, Shen N, Vyse TJ, Anand V, Gunnarson I, Sturfelt G, et al. Selective IgA deficiency in autoimmune diseases. Molecular medicine (Cambridge, Mass). 2011;17(11-12):1383-96.
18q deletion syndrome
Bonilla FA, Khan DA, Ballas ZK, Chinen J, Frank MM, Hsu JT, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. The Journal of allergy and clinical immunology. 2015.
IgG4 deficiency
Bonilla FA, Khan DA, Ballas ZK, Chinen J, Frank MM, Hsu JT, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. The Journal of allergy and clinical immunology. 2015.
Epidemiology
IgA deficiency is more common in Caucasians.
Yel L. Selective IgA deficiency. Journal of clinical immunology. 2010;30:10-6.
Country Prevalence
Arabian peninsula 1:143
Spain 1:163
Nigeria 1:252
England 1:875
Brazil 1:965
USA 1:223 to 1:1,000
China 1:2,600 to 1:5,300
Japan 1:14,840 to 1:18,500
Yel L. Selective IgA deficiency. Journal of clinical immunology. 2010;30:10-6.
Phankingthongkum S, Visitsunthorn N, Vichyanond P. IgA deficiency: a report of three cases from Thailand. Asian Pacific journal of allergy and immunology / launched by the Allergy and Immunology Society of Thailand. 2002;20:203-7.
s
Clinical Manifestations
Wide spectrum of clinical findings
• Asymtomatic
• Recurrent sinopulmonary infections
• Gastrointestinal infections and disorders
• Allergic disorder
• Autoimmune conditions
• Malignancies
Yel L. Selective IgA deficiency. Journal of clinical immunology. 2010;30:10-6.
Edwards E, Razvi S, Cunningham-Rundles C. IgA deficiency: clinical correlates and responses to pneumococcal vaccine. Clinical immunology (Orlando, Fla). 2004;111:93-7.
Edwards E, Razvi S, Cunningham-Rundles C. IgA deficiency: clinical correlates and responses to pneumococcal vaccine. Clinical immunology (Orlando, Fla). 2004;111:93-7.
Edwards E, Razvi S, Cunningham-Rundles C. IgA deficiency: clinical correlates and responses to pneumococcal vaccine. Clinical immunology (Orlando, Fla). 2004;111:93-7.
Edwards E, Razvi S, Cunningham-Rundles C. IgA deficiency: clinical correlates and responses to pneumococcal vaccine. Clinical immunology (Orlando, Fla). 2004;111:93-7.
Edwards E, Razvi S, Cunningham-Rundles C. IgA deficiency: clinical correlates and responses to pneumococcal vaccine. Clinical immunology (Orlando, Fla). 2004;111:93-7.
Recurrent sinopulmonary infections
Edwards E, Razvi S, Cunningham-Rundles C. IgA deficiency: clinical correlates and responses to pneumococcal vaccine. Clinical immunology (Orlando, Fla). 2004;111:93-7.
Aghamohammadi A, Cheraghi T, Gharagozlou M, Movahedi M, Rezaei N, Yeganeh M, et al. IgA deficiency: correlation between clinical and immunological phenotypes. Journal of clinical immunology. 2009;29:130-6.
Chipps BE, Talamo RC, Winkelstein JA. IgA deficiency, recurrent pneumonias, and bronchiectasis. Chest. 1978;73:519-26.
Chipps BE, Talamo RC, Winkelstein JA. IgA deficiency, recurrent pneumonias, and bronchiectasis. Chest. 1978;73:519-26.
Gastrointestinal infections and disorders
•Giardia lamblia
•Malabsorption
•Celiac disease
•Ulcerative colitis
•Nodular lymphoid hyperpalsia
Yel L. Selective IgA deficiency. Journal of clinical immunology. 2010;30:10-6.
Gastrointestinal infections and disorders
•Giardia lamblia
•Malabsorption
•Celiac disease
•Ulcerative colitis
•Nodular lymphoid hyperpalsia
Yel L. Selective IgA deficiency. Journal of clinical immunology. 2010;30:10-6.
Eren M, Saltik-Temizel IN, Yuce A, Caglar M, Kocak N. Duodenal appearance of giardiasis in a child with selective immunoglobulin A deficiency. Pediatrics international : official journal of the Japan Pediatric
Society. 2007;49(3):409-11.
Eren M, Saltik-Temizel IN, Yuce A, Caglar M, Kocak N. Duodenal appearance of giardiasis in a child with selective immunoglobulin A deficiency. Pediatrics international : official journal of the Japan Pediatric Society. 2007;49(3):409-11.
Gastrointestinal infections and disorders
•Giardia lamblia
•Malabsorption
•Celiac disease
•Ulcerative colitis
•Nodular lymphoid hyperpalsia
Yel L. Selective IgA deficiency. Journal of clinical immunology. 2010;30:10-6.
Gastrointestinal infections and disorders
•Giardia lamblia
•Malabsorption
•Celiac disease
•Ulcerative colitis
•Nodular lymphoid hyperpalsia
Yel L. Selective IgA deficiency. Journal of clinical immunology. 2010;30:10-6.
Figure 1 Endoscopic appearance of nodular lymphoid hyperplasia.
• In immunodeficiency states
• To compensate functional inadequate intestinal lymphoid tissue.
• NLH result from an accumulation of plasma-cell precursors.
Albuquerque A. Nodular lymphoid hyperplasia in the gastrointestinal tract in adult patients: A review. World journal of gastrointestinal endoscopy. 2014;6:534-40.
Allergic disorder
Edwards E, Razvi S, Cunningham-Rundles C. IgA deficiency: clinical correlates and responses to pneumococcal vaccine. Clinical immunology (Orlando, Fla). 2004;111:93-7.
Aghamohammadi A, Cheraghi T, Gharagozlou M, Movahedi M, Rezaei N, Yeganeh M, et al. IgA deficiency: correlation between clinical and immunological phenotypes. Journal of clinical immunology. 2009;29:130-6.
Autoimmune conditions
•This figure varies from 3.3 % to 33.6 %based on the age range of studied populations .
Singh K, Chang C, Gershwin ME. IgA deficiency and autoimmunity. Autoimmunity reviews. 2014;13:163-77.
Why IgA deficiency may be associated with autoimmunity?
•Genetic factor
: HLA haplotypes 8.1
•Ig A protect against immunity
:IgA interaction with FCR alpha RI
•Anti-bovine immunoprecipitins in IgA def. pt.
Singh K, Chang C, Gershwin ME. IgA deficiency and autoimmunity. Autoimmunity reviews. 2014;13:163-77.
Why IgA deficiency may be associated with autoimmunity?
•Genetic factor
: HLA haplotypes 8.1
•Ig A protect against immunity
:IgA interaction with FCR alpha RI
•Anti-bovine immunoprecipitins in IgA def. pt.
Singh K, Chang C, Gershwin ME. IgA deficiency and autoimmunity. Autoimmunity reviews. 2014;13:163-77.
Why IgA deficiency may be associated with autoimmunity?
•Genetic factor
: HLA haplotypes 8.1
•Ig A protect against immunity
:IgA interaction with FCR alpha RI
•Anti-bovine immunoprecipitins in IgA def. pt.
Singh K, Chang C, Gershwin ME. IgA deficiency and autoimmunity. Autoimmunity reviews. 2014;13:163-77.
Mkaddem SB, Christou I, Rossato E, Berthelot L, Lehuen A, Monteiro RC.In IgA, IgA receptors, and their anti-inflammatory properties In : Daëron M, Nimmerjahn F,editors :Current Topics in Microbiology and
Immunology . 1st ed. Switzerland Springer International Publishing; 2014. p221-35 .
Inhibition
Fig. 1 a Schematic representation of immunoglobulin A (IgA) binding to the Fc alpha RI–FcRc-chain
Why IgA deficiency may be associated with autoimmunity?
•Genetic factor
: HLA haplotypes 8.1
•Ig A protect against immunity
:IgA interaction with FCR alpha RI
•Anti-bovine immunoprecipitins in IgA def. pt.
Singh K, Chang C, Gershwin ME. IgA deficiency and autoimmunity. Autoimmunity reviews. 2014;13:163-77.
Autoimmune conditions
Edwards E, Razvi S, Cunningham-Rundles C. IgA deficiency: clinical correlates and responses to pneumococcal vaccine. Clinical immunology (Orlando, Fla). 2004;111:93-7.
Edwards E, Razvi S, Cunningham-Rundles C. IgA deficiency: clinical correlates and responses to pneumococcal vaccine. Clinical immunology (Orlando, Fla). 2004;111:93-7.
Aghamohammadi A, Cheraghi T, Gharagozlou M, Movahedi M, Rezaei N, Yeganeh M, et al. IgA deficiency: correlation between clinical and immunological phenotypes. Journal of clinical immunology. 2009;29:130-6.
Wang N, Shen N, Vyse TJ, Anand V, Gunnarson I, Sturfelt G, et al. Selective IgA deficiency in autoimmune diseases. Molecular medicine (Cambridge, Mass). 2011;17:1383-96.
Wang N, Shen N, Vyse TJ, Anand V, Gunnarson I, Sturfelt G, et al. Selective IgA deficiency in autoimmune diseases. Molecular medicine (Cambridge, Mass). 2011;17:1383-96.
Wang N, Shen N, Vyse TJ, Anand V, Gunnarson I, Sturfelt G, et al. Selective IgA deficiency in autoimmune diseases. Molecular medicine (Cambridge, Mass). 2011;17:1383-96.
Wang N, Shen N, Vyse TJ, Anand V, Gunnarson I, Sturfelt G, et al. Selective IgA deficiency in autoimmune diseases. Molecular medicine (Cambridge, Mass). 2011;17:1383-96.
Wang N, Shen N, Vyse TJ, Anand V, Gunnarson I, Sturfelt G, et al. Selective IgA deficiency in autoimmune diseases. Molecular medicine (Cambridge, Mass). 2011;17:1383-96.
Wang N, Shen N, Vyse TJ, Anand V, Gunnarson I, Sturfelt G, et al. Selective IgA deficiency in autoimmune diseases. Molecular medicine (Cambridge, Mass). 2011;17:1383-96.
Celiac Disease
Fasano A, Catassi C. Clinical practice. Celiac disease. The New England journal of medicine. 2012;367:2419-26.
Celiac Disease
Fasano A, Catassi C. Clinical practice. Celiac disease. The New England journal of medicine. 2012;367:2419-26.
Anti IgA antibody
Feng ML, Zhao YL, Shen T, Huang H, Yin B, Liu RZ, et al. Prevalence of immunoglobulin A deficiency in Chinese blood donors and evaluation of anaphylactic transfusion reaction risk. Transfusion medicine (Oxford,
England). 2011;21:338-43.
Malignancies
Edwards E, Razvi S, Cunningham-Rundles C. IgA deficiency: clinical correlates and responses to pneumococcal vaccine. Clinical immunology (Orlando, Fla). 2004;111:93-7.
Table 2 Malignancies and person-years
Ludvigsson JF, Neovius M, Ye W, Hammarstrom L. IgA deficiency and risk of cancer: a population-based
matched cohort study. Journal of clinical immunology. 2015;35:182-8.
Table 2 Malignancies and person-years
Ludvigsson JF, Neovius M, Ye W, Hammarstrom L. IgA deficiency and risk of cancer: a population-based
matched cohort study. Journal of clinical immunology. 2015;35:182-8.
Table 2 Malignancies and person-years
Ludvigsson JF, Neovius M, Ye W, Hammarstrom L. IgA deficiency and risk of cancer: a population-based
matched cohort study. Journal of clinical immunology. 2015;35:182-8.
Fig. 1 Malignancies in IgAD(IgA deficiency) patients andmatched general populationcomparators over 25 years offollow-up
• During follow-up• 125 pts with IgA def.
(61/10,000 person-years) • 984 controls (47/10,000
person-years) • Developed cancer • HR 1.31; 95%CI = 1.09-1.58
Ludvigsson JF, Neovius M, Ye W, Hammarstrom L. IgA deficiency and risk of cancer: a population-based
matched cohort study. Journal of clinical immunology. 2015;35:182-8.
Table 2 Malignancies and person-years :Conditional hazard ratio
Ludvigsson JF, Neovius M, Ye W, Hammarstrom L. IgA deficiency and risk of cancer: a population-based
matched cohort study. Journal of clinical immunology. 2015;35:182-8.
Laboratory Evaluation
IgA deficiency should be a consideration in a patient with…?
•Recurrent respiratory infections
•Recurrent gastrointestinal infections
•Allergic disorders
•Autoimmune disorders
Yel L. Selective IgA deficiency. Journal of clinical immunology. 2010;30:10-6.
Immunologic evaluation for IgA deficiency is also warranted in…?
•Case of anaphylaxis secondary to a blood product transfusion
•Celiac disease
•Family history of IgA deficiency and/or CVID.
Yel L. Selective IgA deficiency. Journal of clinical immunology. 2010;30:10-6.
Hammarstrom L, Vorechovsky I, Webster D. Selective IgA deficiency (SIgAD) and common variable immunodeficiency (CVID). Clinical and experimental immunology. 2000;120:225-31.
Evaluation of a suspected IgA deficiency
•Complete blood count
•Quantitative serum immunoglobulin levels
•Serum IgG subclasses
•Specific antibody response to protein & polysaccharide antigens
•Lymphocyte subsets
Yel L. Selective IgA deficiency. Journal of clinical immunology. 2010;30:10-6.
Definition
•Male or female greater than 4 years of age
•Serum IgA of less than 7 mg/dL (0.07 g/L)
•Normal serum IgG and IgM
•Other causes of hypogammaglobulinemia have
been excluded
•Normal IgG antibody response to vaccination
Conley ME, Notarangelo LD, Etzioni A. Diagnostic criteria for primary immunodeficiencies. Representing PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies). Clinical immunology (Orlando, Fla). 1999;93:190-7.
Ballas ZK, Chinen J, Frank MM, Hsu JT, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. The Journal of allergy and clinical immunology. 2015.
Management
Asymptomatic IgA deficiency
1. Do not need any treatment
2. Awareness & Education to prevent anaphylactic
reaction from blood transfusion
2.1 Wear a medical alert bracelet
2.2 Receive washed normal donor erythrocytes or
blood product from IgA def. person
Yel L. Selective IgA deficiency. Journal of clinical immunology. 2010;30:10-6.Buckley RH,Orange JS. Primary Immunodeficiency Diseases In: Adkinson NF,Bochner BS, Burks AW, Busse WW,Holgate ST, Lemanske RF, O’Hehir RE, editors. Middleton’s allergy: principles & practice. 8 th ed. Philadelphia: Mosby-Elsevier; 2014.
p.1144-74.
Asymptomatic IgA deficiency
1. Do not need any treatment
2. Awareness & Education to prevent anaphylactic
reaction from blood transfusion
2.1 Wear a medical alert bracelet
2.2 Receive washed normal donor erythrocytes or
blood product from IgA def. person
Yel L. Selective IgA deficiency. Journal of clinical immunology. 2010;30:10-6.Buckley RH,Orange JS. Primary Immunodeficiency Diseases In: Adkinson NF,Bochner BS, Burks AW, Busse WW,Holgate ST, Lemanske RF, O’Hehir RE, editors. Middleton’s allergy: principles & practice. 8 th ed. Philadelphia: Mosby-Elsevier; 2014.
p.1144-74.
• The patient has sIgAD
• The patient is at risk for an allergic reaction to
any injected plasma-containing blood products
& testing for anti-IgA antibodies should be
performed before such blood products are
administered.
Medical Alert Bracelet
• 19-year-old woman • End-stage Type 2 autoimmune hepatitis required liver transplantation• She also had sIgAD, anti-IgA antibodies• Episodes of anaphylaxis after receiving IgA-containing blood products • Plan tx with Liver transplantation
Kiani-Alikhan S, Yong PF, Grosse-Kreul D, Height SE, Mijovic A, Suddle AR, et al. Successful desensitization to
immunoglobulin A in a case of transfusion-related anaphylaxis. Transfusion. 2010;50:1897-901.
Time(hr)
Pentaglobin6 mg/mL IgA
Concentration
Rate
0.5 10-7 0.4 ml/kg/hr
1.0 10-6 0.4 ml/kg/hr
1.5 10-5 0.4 ml/kg/hr
2.0 10-4 0.4 ml/kg/hr
2.5 10-3 0.4 ml/kg/hr
3.0 10-2 0.4ml/kg/hr
3.5 10-1 0.4ml/kg/hr
4.0 10-0 32 ml /hr (100 ml)
Immunoglobulin A desensitization Protocol day 1
• Day 2 :Standard Plts IV infusion of 3 mL ->30 mL->300 mL• Day 3 :Standard FFP 3 units• Day 4 & 5 :Standard RBCs3 units with no adverse reactions• Day… :Weekly IV infusions of IgA-enriched immunoglobulins continue
until after a successful liver transplantation
Kiani-Alikhan S, Yong PF, Grosse-Kreul D, Height SE, Mijovic A, Suddle AR, et al. Successful desensitization to
immunoglobulin A in a case of transfusion-related anaphylaxis. Transfusion. 2010;50:1897-901.
Indication for Screening anti IgA Autoantibody
1. Severe sIgAD
2. Partial sIgAD (and other pts) who have
experienced an infusion reaction to a blood
product
IgA deficiency with Associate disease
1. Recurrent infections :Prophylactic antibiotics
2. Allergic disorder : Standard treatment
3. Autoimmune condition : Standard treatment
Yel L. Selective IgA deficiency. Journal of clinical immunology. 2010;30:10-6.Buckley RH,Orange JS. Primary Immunodeficiency Diseases In: Adkinson NF,Bochner BS, Burks AW, Busse WW,Holgate ST, Lemanske RF, O’Hehir RE, editors. Middleton’s allergy: principles & practice. 8 th ed. Philadelphia: Mosby-Elsevier; 2014.
p.1144-74.
Vaccination and IgA deficiency
Contraindicated Vaccines
Risk-SpecificRecommended Vaccines
Effectiveness & Comments
-OPV-BCG-Yellow fever-Other live vaccines appear to be safe.
Pneumococcal All vaccines likely effective. Immuneresponse might be attenuated.
http://www.cdc.gov/vaccines/pubs/pinkbook/downloads/appenciec/A/immuno-table.pdf
Immunoglobulin Replacement Therapy
•Recurrent infections &Poor quality of life
•Fail aggressive ATB therapy & prophylaxis
• Intolerable side effects or hypersensitivity to ATB
Bonilla FA, Khan DA, Ballas ZK, Chinen J, Frank MM, Hsu JT, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. The Journal of allergy and clinical immunology. 2015.
Novel Therapy
•Stimulation CD40/anti CD40 together
with IL-4 & IL 10
• IL-21
Wang N, Hammarstrom L. IgA deficiency: what is new? Current opinion in allergy and clinical immunology. 2012;12(6):602-8.
Prognosis
Clinical heterogeneity and reversibility of selective immunoglobulin A deficiency in 80 children.
Plebani A, Ugazio AG, Monafo V, Burgio GR. Clinical heterogeneity and reversibility of selective immunoglobulin A deficiency in 80 children. Lancet (London, England). 1986:829-31.
40 children with severe sIgAD
40 children with partial sIgAD
Serum IgA level remain low
20 children Serum IgA level return normal
4 Years F/U
Aghamohammadi A, Mohammadi J, Parvaneh N, Rezaei N, Moin M, Espanol T, et al. Progression of selective IgA deficiency to common variable immunodeficiency. International archives of allergy and immunology. 2008;147:87-92
Time of Progression from Selective IgA Def to CVID from 7 months to 27 years
Take Home Message
•IgA deficiency is the most common PID.
•Decreased serum IgA level in the presence of
normal level of other Ig isotype.
•Most individuals with IgA deficiency are
asymptomatic.
Take Home Message
•Some patient may present with
: Recurrent infections of the respiratory &
gastrointestinal tracts
: Allergic disorders
: Autoimmune manifestations
Take Home Message
•Asymptomatic pts
:Education about the condition
:Periodic monitoring
Take Home Message
•Symptomatic patients
:Prophylactic antibiotics
:Vaccine (Pneumococcal vaccine)
:Immunoglobulin
:Standard tx Allergic and Autoimmune condition
:Prevent anaphylactic reaction from blood transfusion