5
Review article J Korean Soc Pediatr Nephrol 2013;17:1-5 DOI: http://dx.doi.org/10.3339/jkspn.2013.17.1.1 Copyright ยฉ 2013 The Korean Society of Pediatric Nephrology ISSN 1226-5292 (print) ISSN 2234-4209 (online) C3 ์‹ ์—ผ์˜ ๋ณ‘๋ฆฌ ์˜๋‚จ๋Œ€ํ•™๊ต ์˜๊ณผ๋Œ€ํ•™ ๋ณ‘๋ฆฌํ•™๊ต์‹ค ๊น€ ์šฉ ์ง„ Pathology of C3 Glomerulonephritis C3 glomerulonephritis (C3GN) is a recently described entity that shows a glo- merulonephritis on light microscopy, bright C3 staining and the absence of C1q, C4, and immunoglobulins on immunofluorescence microscopy and mesangial and/or subendothelial electron-dense deposits on electron microscopy. The term โ€˜C3 glomerulopathyโ€™ is often used to include C3GN and dense deposit disease (DDD), CFHR5 nephropathy, those of which result from dysregulation of the alternative pathway of complement. C3GN shares some aspects of atypical hemolytic uremic syndrome, MPGN, late stage of post infectious glomerulonephritis and other glomerulonephrtis. When C3GN is considered, measurement of serum complement proteins including C3, CFH, CFI, CFB and testing for the presence of C3 nephritic factor, anti-factor H autoantibodies are necessary. To screening for mutations, genes that encode complement regulators should be evaluated. This disorder equally affected all ages, both genders, and typically presented with hematuria and proteinuria. In both the short and long term, renal function remained stable in the majority of patients. Key words: C3 glomerulonephritis, C3 glomerulonephropathy, alternative complement pathway, pathology Yong-Jin Kim Department of Pathology, Yeungnam University College of Medicine, Daegu, Korea Corresponding Author: Yong-Jin Kim Department of Pathology, Yeungnam University College of Medicine, Daegu, Korea Tel: 053-620-3331, Fax: 053-656-1429 E-mail: [email protected] Received: 15 March 2013 Revised: 21 March 21013 Accepted: 25 March 2013 This is an open-access article distributed under the terms of the Creative Commons Attribu- tion Non-Commercial License (http:// crea- tivecommons.org/licenses/bync/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. ์„œ๋ก  2007๋…„ Servais ๋“ฑ[1]์€, ์šฉํ˜ˆ์„ฑ ์š”๋… ์ฆํ›„๊ตฐ(hemolytic uremic syndrome, HUS)๊ณผ ๊ฐ™์€ ์œ ์ „์  ์†Œ์ธ์„ ๊ฐ–๋Š” ์‚ฌ๊ตฌ์ฒด ์‹ ์—ผ ์ค‘, ์ผ๋ฐ˜์ ์ธ HUS์™€๋Š” ๋‹ฌ๋ฆฌ, ๋Œ€์ฒด๋ณด์ฒด๊ฒฝ๋กœ(alternative complement pathway)๊ฐ€ ํ™œ์„ฑํ™”๋˜๊ณ , ์‚ฌ๊ตฌ์ฒด์— ๋ณด ์ฒด3 (C3)์ด ์นจ์ฐฉ๋˜๋Š” ์ƒˆ๋กœ์šด ์‚ฌ๊ตฌ์ฒด ์‹ ์—ผ์„ ์ˆ˜์ง‘ ์ •๋ฆฌํ•˜์˜€๋‹ค. ๊ด‘ํ•™ํ˜„๋ฏธ๊ฒฝ์  ๋ณ€ํ™”๋ณด๋‹ค๋Š”, ๋ฉด์—ญํ˜•๊ด‘ํ˜„๋ฏธ๊ฒฝ ์ƒ C3์˜ ์นจ์ฐฉ์ด ํŠน์ง•์ž„์œผ๋กœ, C3 ์‚ฌ๊ตฌ์ฒด์‹ ์—ผ(C3 glomerulonephritis, C3GN)์œผ๋กœ ๋ช…๋ช…ํ•˜์˜€๋‹ค. ๊ทธ๋Ÿฌ๋‚˜ ๊ธฐ์กด ์‚ฌ๊ตฌ์ฒด ์งˆํ™˜์—์„œ ๋„, C3๋งŒ ์นจ์ฐฉ๋˜๋Š” ๋น„์ „ํ˜•์ ์ธ ์˜ˆ๋“ค์ด ์žˆ์–ด์„œ, ์ด๋“ค์„ C3GN๊ณผ ๊ฐ๋ณ„ํ•˜์—ฌ ์žฌ ๋ถ„๋ฅ˜ํ•˜๊ณ  ์žˆ๋‹ค. ๋ณธ ๋…ผ๋ฌธ์—์„œ๋Š” ์ง€๊ธˆ๊นŒ์ง€ ๋ฐœํ‘œ๋œ ๋ฌธํ—Œ๋“ค์„ ์ •๋ฆฌํ•˜์—ฌ, C3GN์˜

Review articlechikd.org/upload/kjpn-17-1-1-.pdf5) Sethi S, Fervenza FC. Membranoproliferative glomerulone-phritis-a new look at an old entity. N Engl J Med 2012;366: 1119-31. 6) Sethi

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Page 1: Review articlechikd.org/upload/kjpn-17-1-1-.pdf5) Sethi S, Fervenza FC. Membranoproliferative glomerulone-phritis-a new look at an old entity. N Engl J Med 2012;366: 1119-31. 6) Sethi

Review articleJ Korean Soc Pediatr Nephrol 2013;17:1-5DOI: http://dx.doi.org/10.3339/jkspn.2013.17.1.1

Copyright ยฉ 2013 The Korean Society of Pediatric Nephrology

ISSN 1226-5292 (print)ISSN 2234-4209 (online)

C3 ์‹ ์—ผ์˜ ๋ณ‘๋ฆฌ์˜๋‚จ๋Œ€ํ•™๊ต ์˜๊ณผ๋Œ€ํ•™ ๋ณ‘๋ฆฌํ•™๊ต์‹ค

๊น€ ์šฉ ์ง„

Pathology of C3 Glomerulonephritis

C3 glomerulonephritis (C3GN) is a recently described entity that shows a glo-merulonephritis on light microscopy, bright C3 staining and the absence of C1q, C4, and immunoglobulins on immunofluorescence microscopy and mesangial and/or subendothelial electron-dense deposits on electron microscopy. The term โ€˜C3 glomerulopathyโ€™ is often used to include C3GN and dense deposit disease (DDD), CFHR5 nephropathy, those of which result from dysregulation of the alternative pathway of complement. C3GN shares some aspects of atypical hemolytic uremic syndrome, MPGN, late stage of post infectious glomerulonephritis and other glomerulonephrtis. When C3GN is considered, measurement of serum complement proteins including C3, CFH, CFI, CFB and testing for the presence of C3 nephritic factor, anti-factor H autoantibodies are necessary. To screening for mutations, genes that encode complement regulators should be evaluated. This disorder equally affected all ages, both genders, and typically presented with hematuria and proteinuria. In both the short and long term, renal function remained stable in the majority of patients.

Key words: C3 glomerulonephritis, C3 glomerulonephropathy, alternative complement pathway, pathology

Yong-Jin Kim

Department of Pathology, Yeungnam University College of Medicine, Daegu, Korea

Corresponding Author: Yong-Jin KimDepartment of Pathology, Yeungnam University College of Medicine, Daegu, KoreaTel: 053-620-3331, Fax: 053-656-1429E-mail: [email protected]

Received: 15 March 2013Revised: 21 March 21013Accepted: 25 March 2013

This is an open-access article distributed under the terms of the Creative Commons Attribu-tion Non-Commercial License (http:// crea-tivecom mons.org/licenses/bync/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

์„œ๋ก 

2007๋…„ Servais ๋“ฑ[1]์€, ์šฉํ˜ˆ์„ฑ ์š”๋… ์ฆํ›„๊ตฐ(hemolytic uremic syndrome,

HUS)๊ณผ ๊ฐ™์€ ์œ ์ „์  ์†Œ์ธ์„ ๊ฐ–๋Š” ์‚ฌ๊ตฌ์ฒด ์‹ ์—ผ ์ค‘, ์ผ๋ฐ˜์ ์ธ HUS์™€๋Š” ๋‹ฌ๋ฆฌ,

๋Œ€์ฒด๋ณด์ฒด๊ฒฝ๋กœ(alternative complement pathway)๊ฐ€ ํ™œ์„ฑํ™”๋˜๊ณ , ์‚ฌ๊ตฌ์ฒด์— ๋ณด

์ฒด3 (C3)์ด ์นจ์ฐฉ๋˜๋Š” ์ƒˆ๋กœ์šด ์‚ฌ๊ตฌ์ฒด ์‹ ์—ผ์„ ์ˆ˜์ง‘ ์ •๋ฆฌํ•˜์˜€๋‹ค. ๊ด‘ํ•™ํ˜„๋ฏธ๊ฒฝ์ 

๋ณ€ํ™”๋ณด๋‹ค๋Š”, ๋ฉด์—ญํ˜•๊ด‘ํ˜„๋ฏธ๊ฒฝ ์ƒ C3์˜ ์นจ์ฐฉ์ด ํŠน์ง•์ž„์œผ๋กœ, C3 ์‚ฌ๊ตฌ์ฒด์‹ ์—ผ(C3

glomerulonephritis, C3GN)์œผ๋กœ ๋ช…๋ช…ํ•˜์˜€๋‹ค. ๊ทธ๋Ÿฌ๋‚˜ ๊ธฐ์กด ์‚ฌ๊ตฌ์ฒด ์งˆํ™˜์—์„œ

๋„, C3๋งŒ ์นจ์ฐฉ๋˜๋Š” ๋น„์ „ํ˜•์ ์ธ ์˜ˆ๋“ค์ด ์žˆ์–ด์„œ, ์ด๋“ค์„ C3GN๊ณผ ๊ฐ๋ณ„ํ•˜์—ฌ ์žฌ

๋ถ„๋ฅ˜ํ•˜๊ณ  ์žˆ๋‹ค. ๋ณธ ๋…ผ๋ฌธ์—์„œ๋Š” ์ง€๊ธˆ๊นŒ์ง€ ๋ฐœํ‘œ๋œ ๋ฌธํ—Œ๋“ค์„ ์ •๋ฆฌํ•˜์—ฌ, C3GN์˜

Page 2: Review articlechikd.org/upload/kjpn-17-1-1-.pdf5) Sethi S, Fervenza FC. Membranoproliferative glomerulone-phritis-a new look at an old entity. N Engl J Med 2012;366: 1119-31. 6) Sethi

2 J Korean Soc Pediatr Nephrol Vol. 17, No. 1, 1-5, 2013

์ •์˜๋ฅผ ๋ถ„๋ช…ํžˆ ํ•˜์—ฌ ์ง„๋‹จ์˜ ํ˜ผ๋ˆ์„ ๋ง‰๊ณ , ์•„์šธ๋Ÿฌ ๊ธฐ์กด ์‚ฌ๊ตฌ

์ฒด์‹ ์—ผ์—์„œ C3GN๋ฅผ ๋‹ค์‹œ ๋ถ„๋ฅ˜ํ•˜๋Š” ์—ฐ๊ตฌ์— ๋„์›€์ด ๋˜๊ณ ์ž

ํ•œ๋‹ค.

C3GN์˜ ์ •์˜

Servais ๋“ฑ[1]์€ ๋ฉด์—ญํ˜•๊ด‘ ํ˜„๋ฏธ๊ฒฝ ๊ฒ€์‚ฌ์—์„œ C3๋งŒ ๊ฐ•ํ•˜

๊ฒŒ ์—ผ์ƒ‰๋˜๋Š” ๊ฒƒ์„ ํŠน์ง•์œผ๋กœ ๋ถ„๋ฅ˜ํ•˜๊ธฐ๋ฅผ ์ œ์•ˆํ•˜์˜€๋‹ค. ๋”ฐ๋ผ

์„œ ๋‹ค๋ฅธ ๋ฉด์—ญ ๊ธ€๋กœ๋ถˆ๋ฆฐ์ด๋‚˜ ๋ณด์ฒด1q ํ˜น์€ ๋ณด์ฒด4 ๋“ฑ์˜ ์นจ์ฐฉ

์€ ๊ด€์ฐฐ๋˜์ง€ ์•Š์•„์•ผ ํ•œ๋‹ค. ๊ด‘ํ•™ ํ˜„๋ฏธ๊ฒฝ ๊ด€์ฐฐ์—์„œ๋Š” ์‚ฌ๊ตฌ

์ฒด ์„ธํฌ์˜ ์ฆ์‹์ด ์žˆ๋Š” ๊ฒฝ์šฐ๋„ ์žˆ๊ณ  ์—†๋Š” ๊ฒฝ์šฐ๋„ ์žˆ์œผ๋ฉฐ,

์ „์žํ˜„๋ฏธ๊ฒฝ์œผ๋กœ๋Š” ์ „์ž๋ฐ€๋„๊ฐ€ ๋†’์€ ๋ฌผ์งˆ(electron dense

deposit, EDD)์˜ ์นจ์ฐฉ์ด ๋ฉ”์‚ฐ์ง€์›€์— ํ˜น์€ ๋‚ดํ”ผ์„ธํฌ ๋ฐ‘์œผ

๋กœ ๊ด€์ฐฐ๋˜๋ฉฐ, ๋‘ ๊ตฐ๋ฐ ๋ชจ๋‘์—์„œ ๊ด€์ฐฐ๋˜๊ธฐ๋„ ํ•œ๋‹ค.

C3GN์˜ ํ˜•ํƒœํ•™์  ํŠน์ง•๊ณผ ๊ฐ๋ณ„์ 

์‚ฌ๊ตฌ์ฒด ์„ธํฌ์˜ ์ฆ์‹์ด ์žˆ๋Š” ๊ฒฝ์šฐ์™€ ์—†๋Š” ๊ฒฝ์šฐ๋กœ ๋‚˜๋ˆŒ

์ˆ˜ ์žˆ๋‹ค. ์ฆ์‹์ด ์žˆ๋Š” ํ˜•์—์„œ๋Š” ๊ธฐ์กด ๋ง‰์ฆ์‹์„ฑ ์‚ฌ๊ตฌ์ฒด์‹ 

์—ผ(membranoproliferative glomerulonephritis, MPGN)

๊ณผ ์œ ์‚ฌํ•œ ์†Œ๊ฒฌ์„ ๋ณด์ด๋ฉฐ(Fig. 1), ๋ฐ˜๋ฉด ์ฆ์‹์ด ์—†๋Š” C3GN

๋Š” HUS, ๋ณ‘๋ฆฌํ•™์ ์œผ๋กœ๋Š” ํ˜ˆ์ „๋ฏธ์„ธํ˜ˆ๊ด€๋ณ‘์ฆ(thrombotic

microangiopathy, TMA)์™€ ์œ ์‚ฌํ•˜๋‹ค(Fig. 2). ์ฆ‰ C3GN๋Š”

ํ˜•ํƒœ์ ์œผ๋กœ HUS์™€ ์ œ 2ํ˜• MPGN (dense deposit disease,

DDD)์˜ ์–‘๊ทน ์‚ฌ์ด์— ์กด์žฌํ•œ๋‹ค๊ณ  ๋ง ํ•  ์ˆ˜ ์žˆ๋‹ค(Fig. 3).

๋˜ํ•œ ์ฆ์‹์ด ์žˆ๋Š” C3GN์˜ ๊ฒฝ์šฐ๋Š”, DDD์˜ ํŠน์ง•์ธ C3

nephritic factor์˜ ๋ฐœ๊ฒฌ ๋นˆ๋„๊ฐ€ ๋†’์•˜์œผ๋ฉฐ, ์ฆ์‹์ด ์—†๋Š” ๊ฒฝ

์šฐ๋Š” HUS์—์„œ์ฒ˜๋Ÿผ, factor H, factor I, MCP(membrane

cofactor protein) ๋Œ์—ฐ๋ณ€์ด ๋“ฑ์ด ๋ฐœ๊ฒฌ๋˜๋Š” ํ™•๋ฅ ์ด ๋†’์•˜๋‹ค

[1, 2]. ์ด์™€ ๊ฐ™์ด ๊ด‘ํ•™ํ˜„๋ฏธ๊ฒฝ์ ์œผ๋กœ ์ „ํ˜•์ ์ธ MPGN์˜ ๋ชจ

์Šต์„ ๋ณด์ด๋”๋ผ๋„ ๋ฉด์—ญํ˜•๊ด‘ ํ˜„๋ฏธ๊ฒฝ ๊ด€์ฐฐ์—์„œ ๋ฉด์—ญ๊ธ€๋กœ๋ถˆ๋ฆฐ

์˜ ์นจ์ฐฉ์€ ์—†๊ณ , C3๋งŒ ์–‘์„ฑ์ธ ๊ฒฝ์šฐ, C3GN๋ฅผ ์˜์‹ฌํ•ด์•ผ ํ•˜

๋ฉฐ, ์ž„์ƒ์ ์œผ๋กœ ์ •ํ˜• ํ˜น์€ ๋น„์ •ํ˜• HUS์™€ ์œ ์‚ฌํ•˜๋ฉด์„œ ์‹ ์žฅ

์กฐ์ง๊ฒ€์‚ฌ์—์„œ ์‚ฌ๊ตฌ์ฒด์— ์„ธํฌ์˜ ์ฆ์‹์€ ์—†์œผ๋‚˜, ๋ฉด์—ญํ˜•๊ด‘ํ˜„

๋ฏธ๊ฒฝ์—์„œ C3๊ฐ€ ๊ฐ•ํ•˜๊ฒŒ ์นจ์ฐฉ๋œ๋‹ค๋ฉด ์—ญ์‹œ C3GN๋ฅผ ์˜์‹ฌํ•ด ๋ณด

์•„์•ผ๊ฒ ๋‹ค.

Servais ๋“ฑ[1]์ด HUS์™€ ์œ ์‚ฌํ•œ ๊ธฐ์ „์˜ ์‚ฌ๊ตฌ์ฒด ์งˆํ™˜์—์„œ

C3GN๋ฅผ ๊ตฌ๋ถ„ํ•œ ๊ฒฝ์šฐ๋ผ๋ฉด, Sethi ๋“ฑ[3-7]์€ MPGN์˜ ๋น„

ํŠน์ด์  ๋ณ‘๋ฆฌ์†Œ๊ฒฌ์—์„œ C3GN๋ฅผ ๋ถ„๋ฆฌํ•˜๋Š” ์—ฐ๊ตฌ๋“ค์„ ๋ฐœํ‘œํ•˜

์˜€๋‹ค(Fig. 4). MPGN์€ ์‚ฌ๊ตฌ์ฒด ์„ธํฌ์˜ ์ฆ์‹์ด ์žˆ๊ณ , EDD

๊ฐ€ ๋ฉ”์‚ฐ์ง€์›€ ๋ฐ ๋‚ดํ”ผ์„ธํฌ ์•„๋ž˜๋กœ ์นจ์ฐฉํ•˜๋Š” ๊ฒฝ์šฐ๋ฅผ 1ํ˜•, ์‚ฌ

๊ตฌ์ฒด ๊ธฐ์ €๋ง‰ ๋‚ด๋ถ€์— ๋ฆฌ๋ณธ ํ˜•ํƒœ๋กœ ์นจ์ฐฉํ•˜๋Š” ๊ฒฝ์šฐ๋ฅผ 2ํ˜•์œผ

๋กœ ๋ถ„๋ฅ˜ํ•œ๋‹ค[8]. 1ํ˜•์„ ์ข€ ๋” ์ž์„ธํžˆ ๋ณด๋ฉด, ๋ฉด์—ญ๊ธ€๋กœ๋ถˆ๋ฆฐ G

์˜ ์นจ์ฐฉ์„ ํŠน์ง•์œผ๋กœ ํ•˜๋ฉฐ, C3์˜ ์นจ์ฐฉ๋„ ๋ณด์ธ๋‹ค. ์‚ฌ๊ตฌ์ฒด ์„ธ

Fig. 1. C3GN with cellular proliferation. Light microscopically, glomerular changes look like MPGN. Large subendothelial electron dense deposits on EM are positive for C3 on immunofluorescence.

Page 3: Review articlechikd.org/upload/kjpn-17-1-1-.pdf5) Sethi S, Fervenza FC. Membranoproliferative glomerulone-phritis-a new look at an old entity. N Engl J Med 2012;366: 1119-31. 6) Sethi

Kim YJ: Pathology of C3 Glomerulonephritis 3

ํฌ์˜ ์ฆ์‹์ด ์‹ฌํ•˜์—ฌ ์‚ฌ๊ตฌ์ฒด ์†Œ์—ฝ์ด ๊ฐ•์กฐ๋˜์–ด ์žˆ๊ณ (lobular

accentuation), ๊ธฐ์ €๋ง‰์ด ๋‘์ธต์œผ๋กœ ๊ฐˆ๋ผ์ง€๋ฉด์„œ (doubling)

๋ฉ”์‚ฐ์ง€์›€์ด ๋ฐ€๋ ค๋“ค์–ด๊ฐ€๋Š” ํ˜„์ƒ๋“ค์ด ๋ณด์ธ๋‹ค. ํ˜ˆ์ฒญ C3์™€ C4

์˜ ๊ฐ์†Œ๊ฐ€ ์žˆ์–ด์„œ ์ „ํ˜•์  ๋ณด์ฒด๊ฒฝ๋กœ(classic pathway)์˜ ํ™œ์„ฑ

ํ™”์— ์˜ํ•œ ๋ณ‘๋ณ€์ด๋‹ค. ๋ฐ˜๋ฉด 2ํ˜• MPGN๋Š” 1ํ˜•์— ๋น„ํ•ด ์„ธํฌ์˜

์ฆ์‹์ด ์ ์œผ๋ฉฐ, ๋”ฐ๋ผ์„œ ์†Œ์—ฝ์˜ ๊ฐ•์กฐ๋„ ๋šœ๋ ทํ•˜์ง€ ์•Š๋‹ค. EDD

๊ฐ€ ๊ธฐ์ €๋ง‰์„ ๋”ฐ๋ผ์„œ๋งŒ ์นจ์ฐฉ๋˜์ง€๋งŒ ๊ธฐ์ €๋ง‰์ด ๋‘๊บผ์›Œ ์ง€์ง€๋Š”

์•Š๊ธฐ์—, โ€˜๋ง‰์ฆ์‹์„ฑโ€™์ด๋ผ๊ณ  ๋ถ€๋ฅด๊ธฐ์—๋Š” ๋‹ค์†Œ ๋ฏธํกํ•˜์—ฌ, ์ฃผ๋กœ

dense deposit disease๋กœ ํ†ต์šฉ๋˜๊ณ  ์žˆ๋‹ค. ๋˜ํ•œ 1ํ˜•๊ณผ ๊ฒฐ์ •์ 

์œผ๋กœ ๋‹ค๋ฅธ ์ ์€ ๋ฉด์—ญ ๊ธ€๋กœ๋ถˆ๋ฆฐ์˜ ์นจ์ฐฉ์ด ์—†๊ณ  C3 ์˜ ์นจ์ฐฉ๋งŒ

๊ด€์ฐฐ๋œ๋‹ค. ํ˜ˆ์ฒญ C3์˜ ๊ฐ์†Œ๋งŒ ์žˆ์–ด์„œ ๋Œ€์ฒด๋ณด์ฒด๊ฒฝ๋กœ์˜ ํ™œ์„ฑํ™”

์— ์˜ํ•œ ๊ฒƒ์œผ๋กœ ์ƒ๊ฐํ•œ๋‹ค. Sethi ๋“ฑ[3,4]์€ MPGN์˜ ๋ถ„๋ฅ˜ ๊ธฐ

์ค€์„ โ€˜๋ณด์ฒด ํ™œ์„ฑํ™” ์ธก๋ฉดโ€™์œผ๋กœ ์ ‘๊ทผํ•˜์—ฌ 1ํ˜• MPGN์€ ์ „ํ˜•์ 

๋ณด์ฒด๊ฒฝ๋กœ ํ™œ์„ฑํ™” ์งˆํ™˜์œผ๋กœ, 2ํ˜•์€ ๋Œ€์ฒด๋ณด์ฒด๊ฒฝ๋กœ ํ™œ์„ฑํ™” ์งˆ

ํ™˜์œผ๋กœ ๋ถ„๋ฅ˜ํ•˜์˜€๋‹ค. ๋Œ€์ฒด๋ณด์ฒด๊ฒฝ๋กœ ํ™œ์„ฑํ™” ์งˆํ™˜์€ ํ˜ˆ์ฒญ C3์˜

์ง€์†์ ์ธ ๊ฐ์†Œ๋ฅผ ํŠน์ง•์œผ๋กœ ํ•˜๋ฉฐ, ๋Œ€ํ‘œ์ ์ธ ์งˆํ™˜์ด DDD ์ด

์ง€๋งŒ ๊ธฐ์ €๋ง‰์ด ์•„๋‹Œ ๋ฉ”์‚ฐ์ง€์›€ ํ˜น์€ ๋‚ดํ”ผ์„ธํฌ ์•„๋ž˜๋กœ๋งŒ EDD

๊ฐ€ ์žˆ๋Š” ๋ณ€ํ˜•๋„ ์žˆ์Œ์„ ๊ฐ•์กฐํ•˜๊ณ  ์ด๋ฅผ C3GN๋กœ ๋ถ„๋ฅ˜ํ•˜์˜€๋‹ค.

์ฆ‰ ํ˜•ํƒœ์™€ ์ƒ๊ด€์—†์ด C3์˜ ์‚ฌ๊ตฌ์ฒด ์นจ์ฐฉ์„ ํŠน์ง•์œผ๋กœ ํ•˜๋Š” ๋ชจ

๋“  ์‚ฌ๊ตฌ์ฒด ์งˆํ™˜์€ C3GN์— ์†ํ•œ๋‹ค๋Š” ์ฃผ์žฅ์ด๋‹ค. ์ด๋Ÿฐ ๊ด€์ ์—

์„œ ์ด๋“ค ๋ชจ๋‘๋ฅผ ๋Œ€์ฒด๋ณด์ฒด๊ฒฝ๋กœ ์‹ ์งˆํ™˜(alterantive pathway

glomerular disease)๋ผ๊ณ  ๋ถ€๋ฅด๋Š” ๊ฒƒ์ด ๋” ์ข‹์„ ์ง€๋„ ๋ชจ๋ฅธ๋‹ค.

์ด์ƒ์˜ ์„ค๋ช…์œผ๋กœ, C3GN์˜ ๊ฐœ๋…์ด ์—†๋˜ ์‹œ๊ธฐ์—๋Š” ์ œ 1ํ˜•

MPGN ํ˜•ํƒœ๋ฅผ ์ทจํ•˜๋ฉด์„œ ๋ฉด์—ญ ๊ธ€๋กœ๋ถˆ๋ฆฐ์˜ ์นจ์ฐฉ์ด ์—†๋Š” ๊ฒฝ์šฐ

์—๋„ 1ํ˜• MPGN์œผ๋กœ ์ง„๋‹จ๋˜์—ˆ๊ณ [5], HUS์— ์˜ํ•œ ์‹ ์—ผ์€ ๋ฉด

์—ญ๊ธ€๋กœ๋ถˆ๋ฆฐ์€ ๋ฌผ๋ก  ๋ณด์ฒด์˜ ์นจ์ฐฉ๋„ ์—†์–ด์•ผ ํ•˜๋Š”๋ฐ๋„ C3์˜ ์นจ

์ฐฉ์ด ์žˆ๋Š” ๊ฒฝ์šฐ๋„ ์žˆ์—ˆ์ง€๋งŒ ์ด๋“ค ๋Œ€๋ถ€๋ถ„์ด ๋น„์ •ํ˜• HUS ์‹ ์—ผ

์œผ๋กœ ๋ถ„๋ฅ˜๋˜์—ˆ์„ ๊ฒƒ์ด๋‹ค. ๋˜ํ•œ ๊ฐ์—ผํ›„ ์‚ฌ๊ตฌ์ฒด์‹ ์—ผ์€ ๋ฉด์—ญ๊ธ€

๋กœ๋ถˆ๋ฆฐ G์™€ C3์˜ ์นจ์ฐฉ์ด ํŠน์ง•์ด๋‚˜, ๋ง๊ธฐ์—๋Š” ์„ธํฌ์˜ ์ฆ์‹๋„

์ ์ฐจ ์ค„์–ด์ง€๋ฉด์„œ, ๋ฉด์—ญ๊ธ€๋กœ๋ถˆ๋ฆฐ์˜ ์นจ์ฐฉ ์ •๋„๋„ ์ ์ฐจ ์ ์–ด์ง€

C3 Fig. 2. C3GN without cellular proliferation. Light microscopically, this has minimal change but large subendothelial and mesangial electron dense deposits are revealed on EM examination.

HUS C3GN DDD

MPGN

Serum C3

C3 Nef

CF mutation

Fig. 3. Schematic representation of the spectrum of C3GN and differential points with HUS and DDD. C3GN have characters of either MPGN pattern like DDD or without MPGN pattern like HUS. DDD are characterized by presence of C3 Nef and low serum C3 level. In contrast, HUS has a variety of complement factor (CF)mutations. Those are in between in C3GN, Modified from fig 3 in reference [1].

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4 J Korean Soc Pediatr Nephrol Vol. 17, No. 1, 1-5, 2013

๋ฉฐ ๋ณด์ฒด์˜ ์นจ์ฐฉ๋งŒ ๋šœ๋ ธํ•ด ์ง„๋‹ค. ์ด๋Ÿฐ ํŠน์ง•์„ ๋ณด์ด๋Š” ๊ฒฝ์šฐ์˜

์ผ๋ถ€๋Š” C3GN์ด ์•„๋‹Œ์ง€ ์žฌ๊ฒ€์ฆ ํ•ด ๋ณผ ํ•„์š”๊ฐ€ ์žˆ๋‹ค๊ณ  ์ƒ๊ฐ

ํ•œ๋‹ค.

C3์‹ ์—ผ(C3 glomerulonephritis)๊ณผ C3์‹ ์ฆ(C3 glomerulopathy)์˜ ๊ตฌ๋ถ„

๊ธฐ์กด์˜ ์‚ฌ๊ตฌ์ฒด์‹ ์—ผ๋“ค ์ค‘์— C3GN์— ํ•ฉ๋‹นํ•œ ์งˆํ™˜๋“ค์€

DDD, ์ œ 3ํ˜• MPGN, CFHR5 ์‹ ์ฆ(complement factor H

related protein 5), ๊ฐ์—ผํ›„ ์‚ฌ๊ตฌ์ฒด์‹ ์—ผ์˜ ์ผ๋ถ€ ๋“ฑ์ด ์žˆ๋‹ค.

์ด๋“ค์€ ๋ฉด์—ญ๊ธ€๋กœ๋ถˆ๋ฆฐ์˜ ์นจ์ฐฉ์ด ์—†๊ณ  C3๋งŒ ์–‘์„ฑ์ธ ๊ฒฝ์šฐ๋กœ

์„œ C3GN์˜ ์กฐ๊ฑด์— ํ•ฉ๋‹นํ•œ ์งˆํ™˜์ด์ง€๋งŒ, ์›์ธ์ด ๋ถ„๋ช…ํ•˜๊ณ ,

ํ˜•ํƒœ์ ์œผ๋กœ๋„ ๊ตฌ๋ถ„๋˜๋Š” ํŠน์ง•์ด ์žˆ๋‹ค. ๋”ฐ๋ผ์„œ ์ด์ƒ์˜ ๊ฒฝ์šฐ

๋Š” ๊ธฐ์กด์˜ ๋ณ‘๋ช…์„ ์œ ์ง€ํ•˜๋„๋ก ํ•˜์ง€๋งŒ C3GN์™€ ๋งŽ์€ ๋ถ€๋ถ„์—

์„œ ์ผ์น˜ํ•จ์œผ๋กœ, C3์‹ ์ฆ์œผ๋กœ ๋ถ„๋ฅ˜ํ•˜์—ฌ C3GN์™€ ๊ตฌ๋ถ„ํ•˜๊ธฐ๋กœ

ํ•˜์˜€๋‹ค[9].

C3GN์˜ ๋ณ‘๋ฆฌ๊ธฐ์ „

์ด ์งˆํ™˜์˜ ๋ณ‘๋ฆฌ๊ธฐ์ „์€ ๋Œ€์ฒด๋ณด์ฒด๊ฒฝ๋กœ์˜ ์กฐ์ ˆ์ด์ƒ์ž„์ด ์—ฌ

๋Ÿฌ ์—ฐ๊ตฌ์ž๋“ค์—๊ฒŒ์„œ ์ฆ๋ช…๋˜์—ˆ๋‹ค[1]. ๋ณด์ฒด H ์ธ์ž(complement

factor H, CFH) ๊ฒฐํ•, C3 nephritic factor, CFH, CFI, CMP

์˜ ๋Œ์—ฐ๋ณ€์ด, ํ•ญ CFH ํ•ญ์ฒด ๋“ฑ์ด ๋ณด์ฒด ์กฐ์ ˆ์ด์ƒ์˜ ์›์ธ์œผ

๋กœ ์ธ์ •ํ•˜์˜€๋‹ค[1]. de Cordoba ๋“ฑ[11]์€ CFH์˜ ๊ฒฐํ•์ด

DDD๋ฅผ ์œ ๋ฐœํ•˜๋ฉฐ, ๋น„์ „ํ˜• HUS์—๋Š” ์ด ์š”์†Œ์˜ ๊ฒฐํ•์ด ์—†

์Œ์„ ๋ฐํ˜”์œผ๋ฉฐ, CFH ๋Œ์—ฐ๋ณ€์˜๋ฅผ ์œ ๋„ํ•˜์—ฌ ๋งŒ๋“  DDD ์‹คํ—˜

๋™๋ฌผ์—์„œ ํ˜ˆ์ฒญ C3๊ฐ€ ์ •์ƒ์œผ๋กœ ๋Œ์•„์˜ค๋ฉด ํ˜•ํƒœ์ ์œผ๋กœ๋„ ๋น„

์ „ํ˜• HUS์™€ ๋น„์Šทํ•œ ๋ชจ์–‘์œผ๋กœ ๋ณ€ํ•œ๋‹ค๋Š” ๊ฒƒ์„ ์ฆ๋ช…๋˜์—ˆ๋‹ค.

Pickering ๋“ฑ[12]์€ Cyprus์—์„œ ๋ฐœ๊ฒฌ๋œ CFHR5 ์‹ ์ฆ์—์„œ

hybrid CFHR3-1 ์œ ์ „์ž๊ฐ€ ์ด์™€ ๊ฐ™์€ ๊ฐ€์กฑํ˜• C3GN๋ฅผ ๋งŒ

๋“ ๋‹ค๋Š” ๊ฒƒ์„ ์ฆ๋ช…ํ•˜์˜€๋‹ค.

C3GN์˜ ์ž„์ƒ์–‘์ƒ

์•„์ง ๋ฐœํ‘œ๋œ ์˜ˆ๋“ค์ด ๋งŽ์ง€ ์•Š์•„์„œ ์ผ๋ฐ˜ํ™” ํ•  ์ˆ˜๋Š” ์—†์ง€๋งŒ

Sethi ๋“ฑ[13]์ด 12๋ช…์˜ ํ™˜์ž ๋ถ„์„์— ์˜ํ•˜๋ฉด ํŠน๋ณ„ํ•œ ํ˜ธ๋ฐœ ์—ฐ

๋ น์ด ์—†๊ณ , ๋‚จ๋…€ ์„ฑ๋ณ„์ฐจ๋„ ์—†์—ˆ๋‹ค. ๋Œ€๋ถ€๋ถ„์˜ ํ™˜์ž์—์„œ ๊ณ ํ˜ˆ

์••, ๋‹จ๋ฐฑ๋‡จ, ํ˜ˆ๋‡จ๋ฅผ ๋ณด์˜€์œผ๋ฉฐ ์‹ ์žฅ ๊ธฐ๋Šฅ์ด์ƒ์€ ์‹ฌํ•˜์ง€๋Š” ์•Š

์•˜๋‹ค. ๊ทธ๋Ÿฌ๋‚˜ 3๋ช…์€ ์‹ ๊ธฐ๋Šฅ ๋ถ€์ „์— ๋น ์กŒ์œผ๋ฉฐ, ์ด์‹์„ ๋ฐ›์€

๋‘ ํ™˜์ž์—์„œ ์žฌ๋ฐœ์ด ์ƒ๊ฒผ๋‹ค. ์ด๋Š” Servais ๋“ฑ[1]์˜ 19๋ช… ํ™˜

์ž์˜ ๊ฒฝ์šฐ์™€๋„ ๋น„์Šทํ•œ ๊ฒฐ๊ณผ์˜€๋‹ค. ์น˜๋ฃŒ๋Š” ACE ๊ธธํ•ญ์ œ ๋“ฑ์˜

๋Œ€์ฆ์ ์ด์—ˆ์œผ๋ฉฐ, C5 ํ•ญ์ฒด์ธ eculizumab์œผ๋กœ ์น˜์œ ๋œ ๋ณด๊ณ 

๋„ ์žˆ๋‹ค[14].

MPGN TMA

Ig(+) C3(+/-)

Ig(-) C3(+)

Atypical HUS Classic HUS

MPGN SE, MES

GN C3(+) SE, MES

DDD Intramemb

C3(+) No

C3(-) No

Alternative Pathway Activation C3 glomerulopathy Fig. 4. Differential diagnosis algorism of C3GN from thrombotic microangipathy (TMA) and mem-branoproliferative glomerulonephritis(MPGN). Ig; immunoglobulin deposition, SE; subendothelial electron dense deposit, MES; mesangial electron dense deposit, Intramemb; intramembranous electron dense deposit.

Page 5: Review articlechikd.org/upload/kjpn-17-1-1-.pdf5) Sethi S, Fervenza FC. Membranoproliferative glomerulone-phritis-a new look at an old entity. N Engl J Med 2012;366: 1119-31. 6) Sethi

Kim YJ: Pathology of C3 Glomerulonephritis 5

์š”์•ฝ

์‚ฌ๊ตฌ์ฒด์— ๋ฉด์—ญ๊ธ€๋กœ๋ถˆ๋ฆฐ์€ ์Œ์„ฑ์ด๋ฉด์„œ C3 ๋งŒ ์นจ์ฐฉ๋˜๋Š” ๊ฒฝ

์šฐ, ๋‹ค๋ฅธ ์›์ธ์ด ์—†๋Š” ๊ฒฝ์šฐ C3GN์„ ์˜์‹ฌํ•˜์—ฌ์•ผ ํ•œ๋‹ค. ๊ด‘

ํ•™ํ˜„๋ฏธ๊ฒฝ์œผ๋กœ๋Š” ์„ธํฌ์˜ ์ฆ์‹์ด ์žˆ๋Š” ๊ฒฝ์šฐ์™€ ์—†๋Š” ๊ฒฝ์šฐ๊ฐ€

์žˆ์ง€๋งŒ, ์ „์žํ˜„๋ฏธ๊ฒฝ์œผ๋กœ๋Š” EDD๊ฐ€ ๋‚ดํ”ผ์„ธํฌ ๋ฐ‘์œผ๋กœ ํ˜น์€

๋ฉ”์‚ฐ์ง€์›€ ๋“ฑ์— ์นจ์ฐฉํ•จ์„ ํ™•์ธํ•˜์—ฌ์•ผ ํ•œ๋‹ค. ๋Œ€์ฒด๋ณด์ฒด๊ฒฝ๋กœ

์˜ ์กฐ์ ˆ์ด์ƒ์ด ์›์ธ์ž„์œผ๋กœ ํ˜ˆ์ฒญ C3 ์น˜๋ฅผ ๋น„๋กฏํ•˜์—ฌ CFH,

CFI, CFB ๋“ฑ์„ ์ธก์ •ํ•˜์—ฌ์•ผ ํ•˜๋ฉฐ, C3 nephritic factor, anti-

factor H ์ž๊ฐ€ํ•ญ์ฒด ๋“ฑ์„ ์กฐ์‚ฌํ•˜๋Š” ๊ฒƒ์ด ํ•„์š”ํ•˜๋‹ค. ๋ณด์ฒด ์กฐ

์ ˆ์ด์ƒ์„ ์ผ์œผํ‚ค๋Š” ์œ ์ „์ž ๋Œ์—ฐ๋ณ€์ด๋ฅผ ์กฐ์‚ฌํ•ด ๋ณด์•„์•ผ ํ•œ

๋‹ค. ์˜ˆํ›„๋Š” ์•ˆ์ •์ ์ด์ง€๋งŒ, ์น˜๋ฃŒ๋Š” ๋Œ€์ฆ์ ์ด๋‹ค. ์ด๋ก ์ ์œผ๋กœ

๋ณด์ฒด์˜ ํ™œ์„ฑํ™”๋ฅผ ์ €์ง€ํ•˜๋Š” ์•ฝ์œผ๋กœ ๊ฐ€๋Šฅํ•  ๊ฒƒ์œผ๋กœ ์ƒ๊ฐ๋˜

๋ฉฐ, C5 ํ•ญ์ฒด์ธ eculizumab์œผ๋กœ ์น˜์œ ๋œ ๋ณด๊ณ ๋„ ์žˆ๋‹ค.

References

1) Servais A, Fremeaux-Bacchi V, Lequintrec M, Solomon R, Blouin J, Knebelmann B, et al. Primary glomerulonephritis with isolated C3 deposits: a new entity which shares common genetic risk factors with haemolytic uraemic syndrome. J Med Genet 2007;44:193-9.

2) Servais A, Noel LH, Roumenina LT, Le Quintrec M, Ngo S, Dragon-Durey MA, et al. Acquired and genetic complement abnormalities play a critical role in dense deposit disease and other C3 glomerulopathies. Kidney Int 2012;82:454-64.

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4) Sethi S, Fervenza FC, Zhang Y, Nasr SH, Leung N, Vrana J, et al. Proliferative glomerulonephritis secondary to dysfunction of the alternative pathway of complement. Clin J Am Soc

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