Abstract
Background
Wiskott–Aldrich syndrome (WAS) is an X-linked immunodeficiency characterized by thrombocytopenia and eczema and is caused by a mutation in the WAS gene. WAS has heterogeneous clinical manifestations, and its clinically milder form is called X-linked thrombocytopenia (XLT). Patients with WAS/XLT sometimes have kidney complications, the most common of which is immunoglobulin (Ig)A nephropathy associated with aberrant glycosylation of IgA.
Case diagnosis/treatment
The patient was a 6-year-old girl who was diagnosed with female XLT at the age of 4 years; she presented with microscopic hematuria and proteinuria at a school urinalysis. Her father had thrombocytopenia and IgA nephropathy while in his 20 s. The patient and her father had the same WAS gene mutations. A kidney biopsy was performed, and no abnormal findings were observed by light microscopy. Immunofluorescence analysis revealed a granular pattern of IgG staining along the capillary wall. Electron microscopy revealed small electron-dense deposits in subepithelial lesions. Consequently, we diagnosed her with membranous nephropathy (MN). Tissue PLA2R and THSD7A were negative, and she was judged unlikely to have secondary MN on the basis of blood test findings and IgG staining. We started the administration of angiotensin-converting enzyme inhibitors, and her proteinuria gradually decreased.
Conclusion
To our knowledge, this is the first report of MN in a female WAS/XLT patient. WAS protein expression defects affect all immune system cells; however, the mechanisms underlying the occurrence of autoimmunity are not completely understood. In WAS/XLT patients, MN may develop as a result of increased autoantibody production, similar to other types of immunodeficiency.
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References
Ochs HD, Thrasher AJ (2006) The Wiskott-Aldrich syndrome. J Allergy Clin Immunol 117:725–738. https://doi.org/10.1016/j.jaci.2006.02.005
Ochs HD, Filipovich AH, Veys P, Cowan MJ, Kapoor N (2008) Wiskott-Aldrich syndrome: diagnosis, clinical and laboratory manifestations, and treatment. Biol Blood Marrow Transplant 15:84–90. https://doi.org/10.1016/j.bbmt.2008.10.007
Sudhakar M, Rikhi R, Loganayhan SK, Suri D, Singh S (2021) Autoimmunity in Wiskott-Aldrich syndrome: updated perspectives. Appl Clin Genet 14:363–388. https://doi.org/10.2147/TACG.S213920
Shimizu M, Kanegane H, Wada T, Motoyoshi Y, Morio T, Candotti F, Yacie A (2013) Aberrant glycosylation of IgA in Wiskott-Aldrich syndrome and X-linked thrombocytopenia. J Allergy Clin Immunol 131(587–590):E3. https://doi.org/10.1016/j.jaci.2012.08.040
Ariga T, Takahashi Y, Watanabe T, Tsuneta T, Takekoshi Y, Sakiyama Y, Matsumoto Ishii T (1986) Membranous glomerulonephritis in Wiskott-Aldrich syndrome. Pediatr Int 28:226–231. https://doi.org/10.1111/j.1442-200X.1986.tb00721.x
Liu H, Wang Y, Li Y, Tao L, Zhang Y, He X, Zhou Y, Liu X, Wang Y, Li L (2021) Clinical and genetic analysis of 2 rare cases of Wiskott-Aldrich syndrome from Chinese minorities: two case reports. Medicine 100:e25527. https://doi.org/10.1097/MD.0000000000025527
Uemura O, Nagai T, Ishikura K, Ito S, Hataya H, Gotoh Y, Fujita N, Akioka Y, Kaneko T, Honda M (2014) Creatinine-based equation to estimate the glomerular filtration rate in Japanese children and adolescents with chronic kidney disease. Clin Exp Nephrol 18:626–633. https://doi.org/10.1007/s10157-013-0856-y
Caza TN, Hassen SI, Larsen CP (2020) Renal manifestations of common variable immunodeficiency. Kidney360 1:491–500. https://doi.org/10.34067/KID.0000432020
Massaad MJ, Ramesh N, Geha RS (2013) Wiskott-Aldrich syndrome: comprehensive review. Ann N Y Acad Sci 1285:26–43. https://doi.org/10.1111/nyas.12049
Westernburg L, Larsson M, Hardy SJ, Fernandez C, Thrasher AJ, Severinson E (2005) Wiskott-Aldrich syndrome protein deficiency leads to reduced B-cell adhesion, migration, and homing, and a delayed humoral immune response. Blood 105:1144–1152
Erdei A, Isaak A, Torok K, Sandor N, Kremlitzka M, Prechl J, Bajtay Z (2009) Expression and role of CR1 and CR2 on B and T lymphocytes under physiological and autoimmune conditions. Mol Immunol 46:2767–2773. https://doi.org/10.1016/j.molimm.2009.05.181
Menon S, Valentini RP (2010) Membranous nephropathy in children: clinical presentation and therapeutic approach. Pediatr Nephrol 25:1419–1428. https://doi.org/10.1007/s00467-009-1324-5
Safar-Boueri L, Piya A, Beck LH Jr, Ayalon R (2021) Membranous nephropathy: diagnosis, treatment, and monitoring in the post-PLA3R era. Pediatr Nephrol 36:19–30. https://doi.org/10.1007/s00467-019-04425-1
Andreu N, Pujol-Moix N, Martinez-Lostao L, Oset M, Muniz-Diaz E, Estivill X, Volpini V, Fillat C (2003) Wiskott-Aldrich syndrome in a female with skewed X-chromosome inactivation. Blood Cells Mol Dis 31:332–337. https://doi.org/10.1016/s1079-9796(03)00168-2
Inoue H, Kurosawa H, Nonoyama S, Imai K, Kumazaki H, Matsunaga T, Sato Y, Sugita K, Eguchi M (2002) X-linked thrombocytopenia in a girl. Br J Haematol 118:1163–1165. https://doi.org/10.1016/j.bcmd.2013.04.004
Acknowledgements
The authors thank Drs. Kenichiro Miura and Shigeru Horita for pathological examination of this case; Drs. Kohsuke Imai, Kunio Miyake, Kay Tanita, Kanako Mitsui, and Etsushi Tomifuku for immunological and genetic analyses; and Mr. Mitchell Arico and Dr. Bronwen Gardner from Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript.
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MO was involved in patient care and wrote the manuscript. MN supervised this case and contributed to critical revision of the manuscript. AO contributed to critical revision of the manuscript. HK conducted the patient’s genetic analysis. All authors read and approved the final manuscript.
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Okada, M., Nagasawa, M., Oshiba, A. et al. Membranous nephropathy in a female patient with X-linked thrombocytopenia. Pediatr Nephrol 38, 2873–2876 (2023). https://doi.org/10.1007/s00467-022-05833-6
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DOI: https://doi.org/10.1007/s00467-022-05833-6