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ANTI-Ro/SSA 52 ANTIBODIES IN AUTOIMMUNE DISEASES Coordinator: Monica Copotoiu MD,PhD First author: Gabriela Mihai Coauthors: Isabela Micu, Mihaela Budianu, Andrea Lőrincz

ANTI-Ro/SSA 52 ANTIBODIES IN AUTOIMMUNE DISEASES Coordinator: Monica Copotoiu MD,PhD First author: Gabriela Mihai Coauthors: Isabela Micu, Mihaela Budianu,

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Page 1: ANTI-Ro/SSA 52 ANTIBODIES IN AUTOIMMUNE DISEASES Coordinator: Monica Copotoiu MD,PhD First author: Gabriela Mihai Coauthors: Isabela Micu, Mihaela Budianu,

ANTI-Ro/SSA 52 ANTIBODIES IN

AUTOIMMUNE DISEASES

Coordinator: Monica Copotoiu MD,PhD First author: Gabriela Mihai Coauthors: Isabela Micu, Mihaela Budianu, Andrea

Lőrincz

Page 2: ANTI-Ro/SSA 52 ANTIBODIES IN AUTOIMMUNE DISEASES Coordinator: Monica Copotoiu MD,PhD First author: Gabriela Mihai Coauthors: Isabela Micu, Mihaela Budianu,

Defining criteria for autoimmune diseases

Witebsky's postulatesˡ:

1. An autoimmune reaction is identified in the form of autoantibody or cell-mediated immune reaction

2. The corresponding antigen is known3. An analogous response causes a similar disease

in experimental animals

ˡ Rose, N. R., C. Bona. 1993. Defining criteria for autoimmune diseases (Witebsky’s postulates revisited). Immunol. Today

Page 3: ANTI-Ro/SSA 52 ANTIBODIES IN AUTOIMMUNE DISEASES Coordinator: Monica Copotoiu MD,PhD First author: Gabriela Mihai Coauthors: Isabela Micu, Mihaela Budianu,

Anti-Ro/SSA 52 antibodies(aSSA52)

• aSSA52 are one of the most frequently detected antibodies against Extractable Nuclear Antigen(ENA)ˡ

• Clinically,the presence of aSSA52 has been reported in various rheumatic diseases but also in other autoimmune diseases.

ˡ Ryusule Yoshimi et al. Clinical and Pathological Roles of Ro/SSA Autoantibody System. Clinical and Developmental Immunology Volume 2012

1

Page 4: ANTI-Ro/SSA 52 ANTIBODIES IN AUTOIMMUNE DISEASES Coordinator: Monica Copotoiu MD,PhD First author: Gabriela Mihai Coauthors: Isabela Micu, Mihaela Budianu,

aSSA52 and Autoimmune diseases association

aSSA52 and AD association according to the literatureˡ

Polymyositis/Dermatomyositis (PM/DM)

Systemic Lupus Erythematosus (SLE)

Sjogren syndrome (SjS)

Undifferentiated connective tissue disease (UCTD)

Systemic Sclerosis (SSc)

Rheumatoid Arthritis (RA)

Neonatal Lupus Erythematosus (NLE)

Primary biliary cirrhosis (PBC)

Autoimmune Hepatitis I (AIH I)

ˡDefendenti C et al. Clinical and laboratory aspects of Ro/SSA-52 autoantibodies.Autoimmune Rev 2011 Jan

Page 5: ANTI-Ro/SSA 52 ANTIBODIES IN AUTOIMMUNE DISEASES Coordinator: Monica Copotoiu MD,PhD First author: Gabriela Mihai Coauthors: Isabela Micu, Mihaela Budianu,

aSSA52 detection.Extractable Nuclear Antigen (ENA) panel

Anti-Rnp/Sm Anti-Cenp B

Anti-Sm Anti-PCNA

Anti-SSA(Ro) Anti-DsDNA

Anti-SSA-Ro52 Anti-Nucleosome

Anti-SSB(La) Anti-Histone

Anti-Scl-70 Anti Ribosomal P protein

Anti-PM-Scl Anti AMA-M2

Anti-Jo-1

Page 6: ANTI-Ro/SSA 52 ANTIBODIES IN AUTOIMMUNE DISEASES Coordinator: Monica Copotoiu MD,PhD First author: Gabriela Mihai Coauthors: Isabela Micu, Mihaela Budianu,

Objective

Our purpose is to study the clinical significance and immunological association in patients displaying aSSA52 in various autoimmune diseases(AD).

Page 7: ANTI-Ro/SSA 52 ANTIBODIES IN AUTOIMMUNE DISEASES Coordinator: Monica Copotoiu MD,PhD First author: Gabriela Mihai Coauthors: Isabela Micu, Mihaela Budianu,

Material and Method

• single center• Mureș County Emergency Clinical

Hospital,Rheumatology Division• retrospective and prospective(2013-2015)• 41 patients• ENA immunoblotting panels analysis

Page 8: ANTI-Ro/SSA 52 ANTIBODIES IN AUTOIMMUNE DISEASES Coordinator: Monica Copotoiu MD,PhD First author: Gabriela Mihai Coauthors: Isabela Micu, Mihaela Budianu,

Material and method

Autoimmune Disease (AD) was defined when a patient displayed one of these:

1.Systemic Lupus Erythematosus(SLE)2.Polymyositis/Dermatomyositis(PM/DM)3.Sjogren Syndrome(SjS)4.Rheumatoid Arthritis(RA)5.Systemic Sclerosis(SSc)6.Unedifferentiated Connective tissue disease(UCTD)

Page 9: ANTI-Ro/SSA 52 ANTIBODIES IN AUTOIMMUNE DISEASES Coordinator: Monica Copotoiu MD,PhD First author: Gabriela Mihai Coauthors: Isabela Micu, Mihaela Budianu,

Material and method

Inclusion criteria Exclusion criteria

Page 10: ANTI-Ro/SSA 52 ANTIBODIES IN AUTOIMMUNE DISEASES Coordinator: Monica Copotoiu MD,PhD First author: Gabriela Mihai Coauthors: Isabela Micu, Mihaela Budianu,

Results

Page 11: ANTI-Ro/SSA 52 ANTIBODIES IN AUTOIMMUNE DISEASES Coordinator: Monica Copotoiu MD,PhD First author: Gabriela Mihai Coauthors: Isabela Micu, Mihaela Budianu,

Gender distribution through connective tissue diseases(CTD)

Page 12: ANTI-Ro/SSA 52 ANTIBODIES IN AUTOIMMUNE DISEASES Coordinator: Monica Copotoiu MD,PhD First author: Gabriela Mihai Coauthors: Isabela Micu, Mihaela Budianu,

Gender distribution

Page 13: ANTI-Ro/SSA 52 ANTIBODIES IN AUTOIMMUNE DISEASES Coordinator: Monica Copotoiu MD,PhD First author: Gabriela Mihai Coauthors: Isabela Micu, Mihaela Budianu,

Mean age of onset of CTDs between aSSA52- and aSSA52+ groups

Page 14: ANTI-Ro/SSA 52 ANTIBODIES IN AUTOIMMUNE DISEASES Coordinator: Monica Copotoiu MD,PhD First author: Gabriela Mihai Coauthors: Isabela Micu, Mihaela Budianu,

Distribution of aSSA52 through CTDs

P value=0.058

Page 15: ANTI-Ro/SSA 52 ANTIBODIES IN AUTOIMMUNE DISEASES Coordinator: Monica Copotoiu MD,PhD First author: Gabriela Mihai Coauthors: Isabela Micu, Mihaela Budianu,

Extractable nuclear antigen (ENA) antibodies distribution

Page 16: ANTI-Ro/SSA 52 ANTIBODIES IN AUTOIMMUNE DISEASES Coordinator: Monica Copotoiu MD,PhD First author: Gabriela Mihai Coauthors: Isabela Micu, Mihaela Budianu,

25

2912

22

710

77

22

0 10 20 30 40

Rnp/SmSm

SSARoSSBLaScl 70

PM-SclJo-1

dsDNANucleosom

HistoneRib P prot

AMA-2

ENA

Pan

el a

nti

bo

die

s

Percentage %

aSSA52 associated auto-antibodies

(p-0.01)

(p-0.03)

Page 17: ANTI-Ro/SSA 52 ANTIBODIES IN AUTOIMMUNE DISEASES Coordinator: Monica Copotoiu MD,PhD First author: Gabriela Mihai Coauthors: Isabela Micu, Mihaela Budianu,

Interstitial pulmonary fibrosis (IFP) prevalence in positive and negative aSSA52 groups

12.2%7.3%

58.5%

22%

P-0.059 (ns)

Page 18: ANTI-Ro/SSA 52 ANTIBODIES IN AUTOIMMUNE DISEASES Coordinator: Monica Copotoiu MD,PhD First author: Gabriela Mihai Coauthors: Isabela Micu, Mihaela Budianu,

Distribution of IPF through Connective tissue diseases (CTDs) in aSSA52+ group

Page 19: ANTI-Ro/SSA 52 ANTIBODIES IN AUTOIMMUNE DISEASES Coordinator: Monica Copotoiu MD,PhD First author: Gabriela Mihai Coauthors: Isabela Micu, Mihaela Budianu,

Clinical manifestations in CTDs and aSSA52

Page 20: ANTI-Ro/SSA 52 ANTIBODIES IN AUTOIMMUNE DISEASES Coordinator: Monica Copotoiu MD,PhD First author: Gabriela Mihai Coauthors: Isabela Micu, Mihaela Budianu,

Study limitations

In our study, only a few patients had inclusion criteria (n=41) and the small sample size limits the power of the study.

Differences between aSSA52+ and aSSA52- groups regarding CTDs features were not significant perhaps due to low absolute numbers which limit the statistical analysis.

Page 21: ANTI-Ro/SSA 52 ANTIBODIES IN AUTOIMMUNE DISEASES Coordinator: Monica Copotoiu MD,PhD First author: Gabriela Mihai Coauthors: Isabela Micu, Mihaela Budianu,

Conclusions

• It seems that the presence of aSSA52 are associated with IPF in CTDs.

• The most prevalent autoimmune diseases associating aSSA52 are PM and SLE.

• It is recommended to monitor aSSA52 in patiens diagnosed with CTDs in order to predict the outcome.

Page 22: ANTI-Ro/SSA 52 ANTIBODIES IN AUTOIMMUNE DISEASES Coordinator: Monica Copotoiu MD,PhD First author: Gabriela Mihai Coauthors: Isabela Micu, Mihaela Budianu,