Utility of glomerular Gd-IgA1 staining for indistinguishable cases of IgA nephropathy or Alport syndrome.
Alport syndrome
Galactose-deficient IgA1
Glomerular basement membrane
IgA nephropathy
Journal
Clinical and experimental nephrology
ISSN: 1437-7799
Titre abrégé: Clin Exp Nephrol
Pays: Japan
ID NLM: 9709923
Informations de publication
Date de publication:
Jul 2021
Jul 2021
Historique:
received:
10
12
2020
accepted:
11
03
2021
pubmed:
21
3
2021
medline:
15
12
2021
entrez:
20
3
2021
Statut:
ppublish
Résumé
Pathological findings in Alport syndrome frequently show mesangial proliferation and sometimes incidental IgA deposition, in addition to unique glomerular basement membrane (GBM) changes including thin basement membrane and/or lamellation. However, similar GBM abnormalities are also often observed in IgA nephropathy. Both diseases are also known to show hematuria, proteinuria, and sometimes macrohematuria when associated with viral infection. Therefore, it can be difficult to make a differential diagnosis, even based on clinical and pathological findings. Some recent articles demonstrated that galactose-deficient IgA1 (Gd-IgA1)-specific monoclonal antibody (KM55) could potentially enable incidental IgA deposition to be distinguished from IgA nephropathy. We performed comprehensive gene screening and glomerular Gd-IgA1 and type IV collagen α5 chain immunostaining for five cases with both IgA deposition and GBM changes to confirm that Gd-IgA1 can help to distinguish these two diseases. Four of the cases were genetically diagnosed with Alport syndrome (Cases 1-4) and one was IgA nephropathy with massive GBM changes, which had a negative gene test result (Case 5). In Cases 1-4, glomerular Gd-IgA1 deposition was not detected, although there was positivity for IgA in the mesangial area. In Case 5, glomerular Gd-IgA1 deposition was observed. Gd-IgA1 expression analysis could clearly differentiate these two disorders. This approach can be applied to identify these two diseases showing identical clinical and pathological findings.
Sections du résumé
BACKGROUND
BACKGROUND
Pathological findings in Alport syndrome frequently show mesangial proliferation and sometimes incidental IgA deposition, in addition to unique glomerular basement membrane (GBM) changes including thin basement membrane and/or lamellation. However, similar GBM abnormalities are also often observed in IgA nephropathy. Both diseases are also known to show hematuria, proteinuria, and sometimes macrohematuria when associated with viral infection. Therefore, it can be difficult to make a differential diagnosis, even based on clinical and pathological findings. Some recent articles demonstrated that galactose-deficient IgA1 (Gd-IgA1)-specific monoclonal antibody (KM55) could potentially enable incidental IgA deposition to be distinguished from IgA nephropathy.
METHODS
METHODS
We performed comprehensive gene screening and glomerular Gd-IgA1 and type IV collagen α5 chain immunostaining for five cases with both IgA deposition and GBM changes to confirm that Gd-IgA1 can help to distinguish these two diseases.
RESULTS
RESULTS
Four of the cases were genetically diagnosed with Alport syndrome (Cases 1-4) and one was IgA nephropathy with massive GBM changes, which had a negative gene test result (Case 5). In Cases 1-4, glomerular Gd-IgA1 deposition was not detected, although there was positivity for IgA in the mesangial area. In Case 5, glomerular Gd-IgA1 deposition was observed.
CONCLUSION
CONCLUSIONS
Gd-IgA1 expression analysis could clearly differentiate these two disorders. This approach can be applied to identify these two diseases showing identical clinical and pathological findings.
Identifiants
pubmed: 33743099
doi: 10.1007/s10157-021-02054-3
pii: 10.1007/s10157-021-02054-3
doi:
Substances chimiques
Immunoglobulin A
0
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
779-787Références
Kashtan CE. Alport syndrome and thin glomerular basement membrane disease. J Am Soc Nephrol. 1998;9(9):1736–50.
doi: 10.1681/ASN.V991736
Nozu K, Nakanishi K, Abe Y, Udagawa T, Okada S, Okamoto T, et al. A review of clinical characteristics and genetic backgrounds in Alport syndrome. Clin Exp Nephrol. 2019;23(2):158–68. https://doi.org/10.1007/s10157-018-1629-4 .
doi: 10.1007/s10157-018-1629-4
pubmed: 30128941
Yao XD, Chen X, Huang GY, Yu YT, Xu ST, Hu YL, et al. Challenge in pathologic diagnosis of Alport syndrome: evidence from correction of previous misdiagnosis. Orphanet J Rare Dis. 2012;7:100. https://doi.org/10.1186/1750-1172-7-100 .
doi: 10.1186/1750-1172-7-100
pubmed: 23259488
pmcid: 3552947
Navas-Palacios JJ, Gutierrez-Millet V, Usera-Sarrage G, Garzon-Martin A. IgA nephropathy: an ultrastructural study. Ultrastruct Pathol. 1981;2(2):151–61. https://doi.org/10.3109/01913128109064244 .
doi: 10.3109/01913128109064244
pubmed: 7268925
Ng WL, Chan KW, Yeung CK, Kwan S. Peripheral glomerular capillary wall lesions in IgA nephropathy and their implications. Pathology. 1984;16(3):324–30. https://doi.org/10.3109/00313028409068545 .
doi: 10.3109/00313028409068545
pubmed: 6393013
Taguchi T, von Bassewitz DB, Grundmann E, Takebayashi S. Ultrastructural changes of glomerular basement membrane in IgA nephritis: relationship to hematuria. Ultrastruct Pathol. 1988;12(1):17–26. https://doi.org/10.3109/01913128809048473 .
doi: 10.3109/01913128809048473
pubmed: 3354074
Morita M, Sakaguchi H. A quantitative study of glomerular basement membrane changes in IgA nephropathy. J Pathol. 1988;154(1):7–18. https://doi.org/10.1002/path.1711540103 .
doi: 10.1002/path.1711540103
pubmed: 3346772
Yoshikawa N, Yoshiara S, Yoshiya K, Matsuo T, Okada S. Lysis of the glomerular basement membrane in children with IgA nephropathy and Henoch-Shönlein nephritis. J Pathol. 1986;150(2):119–26. https://doi.org/10.1002/path.1711500206 .
doi: 10.1002/path.1711500206
pubmed: 3794864
Suzuki H, Kiryluk K, Novak J, Moldoveanu Z, Herr AB, Renfrow MB, et al. The pathophysiology of IgA nephropathy. J Am Soc Nephrol. 2011;22(10):1795–803. https://doi.org/10.1681/ASN.2011050464 .
doi: 10.1681/ASN.2011050464
pubmed: 21949093
pmcid: 3892742
Yamasaki K, Suzuki H, Yasutake J, Yamazaki Y, Suzuki Y. Galactose-deficient IgA1-specific antibody recognizes GalNAc-modified unique epitope on hinge region of IgA1. Monoclon Antib Immunodiagn Immunother. 2018;37(6):252–6. https://doi.org/10.1089/mab.2018.0041 .
doi: 10.1089/mab.2018.0041
pubmed: 30570353
pmcid: 6338562
Yasutake J, Suzuki Y, Suzuki H, Hiura N, Yanagawa H, Makita Y, et al. Novel lectin-independent approach to detect galactose-deficient IgA1 in IgA nephropathy. Nephrol Dial Transplant. 2015;30(8):1315–21. https://doi.org/10.1093/ndt/gfv221 .
doi: 10.1093/ndt/gfv221
pubmed: 26109484
pmcid: 4513896
Suzuki H, Yasutake J, Makita Y, Tanbo Y, Yamasaki K, Sofue T, et al. IgA nephropathy and IgA vasculitis with nephritis have a shared feature involving galactose-deficient IgA1-oriented pathogenesis. Kidney Int. 2018;93(3):700–5. https://doi.org/10.1016/j.kint.2017.10.019 .
doi: 10.1016/j.kint.2017.10.019
pubmed: 29329643
Wang M, Lv J, Zhang X, Chen P, Zhao M, Zhang H. Secondary IgA nephropathy shares the same immune features with primary IgA nephropathy. Kidney Int Rep. 2020;5(2):165–72. https://doi.org/10.1016/j.ekir.2019.10.012 .
doi: 10.1016/j.ekir.2019.10.012
pubmed: 32043030
Cassol CA, Bott C, Nadasdy GM, Alberton V, Malvar A, Nagaraja HN, et al. Immunostaining for galactose-deficient immunoglobulin A is not specific for primary immunoglobulin A nephropathy. Nephrol Dial Transplant. 2019. https://doi.org/10.1093/ndt/gfz152 .
doi: 10.1093/ndt/gfz152
Ishiko S, Horinouchi T, Fujimaru R, Shima Y, Kaito H, Tanaka R, et al. Glomerular galactose-deficient IgA1 expression analysis in pediatric patients with glomerular diseases. Sci Rep. 2020;10(1):14026. https://doi.org/10.1038/s41598-020-71101-y .
doi: 10.1038/s41598-020-71101-y
pubmed: 32820208
pmcid: 7441388
Zhao L, Peng L, Yang D, Chen S, Lan Z, Zhu X, et al. Immunostaining of galactose-deficient IgA1 by KM55 is not specific for immunoglobulin A nephropathy. Clin Immunol. 2020;217:108483. https://doi.org/10.1016/j.clim.2020.108483 .
doi: 10.1016/j.clim.2020.108483
pubmed: 32479989
Kamiyoshi N, Nozu K, Fu XJ, Morisada N, Nozu Y, Ye MJ, et al. Genetic, clinical, and pathologic backgrounds of patients with autosomal dominant alport syndrome. Clin J Am Soc Nephrol. 2016;11(8):1441–9. https://doi.org/10.2215/CJN.01000116 .
doi: 10.2215/CJN.01000116
pubmed: 27281700
pmcid: 4974872
Yamamura T, Nozu K, Minamikawa S, Horinouchi T, Sakakibara N, Nagano C, et al. Comparison between conventional and comprehensive sequencing approaches for genetic diagnosis of Alport syndrome. Mol Genet Genomic Med. 2019;7(9):e883. https://doi.org/10.1002/mgg3.883 .
doi: 10.1002/mgg3.883
pubmed: 31364286
pmcid: 6732293
Hashimura Y, Nozu K, Kaito H, Nakanishi K, Fu XJ, Ohtsubo H, et al. Milder clinical aspects of X-linked Alport syndrome in men positive for the collagen IV alpha5 chain. Kidney Int. 2014;85(5):1208–13. https://doi.org/10.1038/ki.2013.479 .
doi: 10.1038/ki.2013.479
pubmed: 24304881
Oka M, Nozu K, Kaito H, Fu XJ, Nakanishi K, Hashimura Y, et al. Natural history of genetically proven autosomal recessive Alport syndrome. Pediatr Nephrol. 2014;29(9):1535–44. https://doi.org/10.1007/s00467-014-2797-4 .
doi: 10.1007/s00467-014-2797-4
pubmed: 24633401
Kamimura H, Honda K, Nitta K, Horita S, Kobayashi H, Uchida K, et al. Glomerular expression of alpha2(IV) and alpha5(IV) chains of type IV collagen in patients with IgA nephropathy. Nephron. 2002;91(1):43–50. https://doi.org/10.1159/000057603 .
doi: 10.1159/000057603
pubmed: 12021518
Masuda Y, Yamanaka N, Ishikawa A, Kataoka M, Arai T, Wakamatsu K, et al. Glomerular basement membrane injuries in IgA nephropathy evaluated by double immunostaining for alpha5(IV) and alpha2(IV) chains of type IV collagen and low-vacuum scanning electron microscopy. Clin Exp Nephrol. 2015;19(3):427–35. https://doi.org/10.1007/s10157-014-1008-8 .
doi: 10.1007/s10157-014-1008-8
pubmed: 25056826
Stapleton CP, Kennedy C, Fennelly NK, Murray SL, Connaughton DM, Dorman AM, et al. An exome sequencing study of 10 families with IgA nephropathy. Nephron. 2020;144(2):72–83. https://doi.org/10.1159/000503564 .
doi: 10.1159/000503564
pubmed: 31865346
Savige J, Ariani F, Mari F, Bruttini M, Renieri A, Gross O, et al. Expert consensus guidelines for the genetic diagnosis of Alport syndrome. Pediatr Nephrol. 2019;34(7):1175–89. https://doi.org/10.1007/s00467-018-3985-4 .
doi: 10.1007/s00467-018-3985-4
pubmed: 29987460
Suzuki K, Honda K, Tanabe K, Toma H, Nihei H, Yamaguchi Y. Incidence of latent mesangial IgA deposition in renal allograft donors in Japan. Kidney Int. 2003;63(6):2286–94. https://doi.org/10.1046/j.1523-1755.63.6s.2.x .
doi: 10.1046/j.1523-1755.63.6s.2.x
pubmed: 12753320