Selective immunoglobulin M deficiency (SIgMD) is the isolated absence of serum immunoglobulin M (IgM) with normal levels of other serum immunoglobulins. SIgMD is associated with infections and autoimmune diseases. While there are few reports on SIgMD complicated by systemic lupus erythematosus (SLE), there are no reports on SIgMD complicated by SLE and antiphospholipid syndrome (APS); we present the first report of this kind. A 61-year-old Japanese woman presented with microscopic hematuria and proteinuria. Clinical investigations revealed an elevated serum creatinine level, an undetectable serum IgM level, and seropositivity of antinuclear antibody, anti-Smith antibody, and double-stranded DNA antibody. Radiological investigations were unremarkable. Renal biopsy revealed focal and segmental mesangial cell proliferation; thickened glomerular capillary walls; and IgG, IgA, C3, and C1q deposition, which indicated class III (A/C) lupus nephritis (Renal Pathology Society/International Society of Nephrology classification). Furthermore, anti-CLβ2GP1 antibody positivity and deep vein thrombosis were noted, which fulfilled the revised Sapporo classification criteria for the diagnosis of APS. Thus, she was diagnosed with SIgMD complicated by SLE and APS. The patient was treated with prednisolone, mycophenolate mofetil, and warfarin. After a 1-year follow-up, she achieved clinical remission of SLE and APS without infectious complications; however, the serum IgM level remained undetectable. In conclusion, SIgMD can be complicated by autoimmune disorders. Although rare, we recommend that SLE and APS be considered in patients with SIgMD who present with hematuria, proteinuria, and deep vein thrombosis. We also recommend measuring the titers of antinuclear antibodies, double-stranded DNA antibodies, and anti-CLβ2GP1 antibodies.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
Tax calculation will be finalised during checkout.
Gupta S, Gupta A. Selective IgM deficiency-an underestimated primary immunodeficiency. Front Immunol. 2017;8:1056.
Lucuab-Fegurgur DL, Gupta S. Comprehensive clinical and immunological features of 62 adult patients with selective primary IgM deficiency. Am J Clin Exp Immunol. 2019;8:55–67.
Ni J, Zhang J, Chen Q, Chen Y, Liu J. The epidemiology and clinical features of selective immunoglobulin M deficiency: a single-center study in China. J Clin Lab Anal. 2020;34:e23289.
Entezari N, Adab Z, Zeydi M, Saghafi S, Jamali M, Kardar GA, et al. The prevalence of selective immunoglobulin M deficiency (SIgMD) in Iranian volunteer blood donors. Hum Immunol. 2016;77:7–11.
Ogura J, Yoshio S, Masuyama J, Kumatani M, Karino S. A case of systemic lupus erythematosus associated with systemic IgM deficiency. Nihon Naikagakkai Zasshi. 1989;78:884–6 (in Japanese).
Sasaki T, Denpo K, Takahashi K, Nakajima H, Kameda H. Systemic lupus erythematosus associated with selective IgM deficiency. Rhinsho Hihuka. 1993;47:249–52 (in Japanese).
Tanaka A, Kasahara M, Miyawaki T, Yahata K, Hashimoto H, Sugawara A, et al. A case of selective IgM deficiency associated with systemic lupus erythematosus. Nihon Jinzo Gakkai Shi. 1996;38:185–90.
Takeuchi T, Nakagawa T, Maeda Y, Hirano S, Sasaki-Hayashi M, Makino S, et al. Functional defect of B lymphocytes in a patient with selective IgM deficiency associated with systemic lupus erythematosus. Autoimmunity. 2001;34:115–22.
Miura T, Honma R, Iida T, Yamagishi Y. A case of systemic lupus erythematosus associated with selective IgM deficiency. Clin Rheumatol Related Res. 2015;27:212–8 (in Japanese).
Weening JJ, D’Agati VD, Schwartz MM, Seshan SV, Alpers CE, Appel GB, et al. The classification of glomerulonephritis in systemic lupus erythematosus revisited. Kidney Int. 2004;65:521–30.
Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006;4:295–306.
Yamasaki T. Selective IgM deficiency: functional assessment of peripheral blood lymphocytes in vitro. Intern Med. 1992;31:866–70.
Mensen A, Karuse T, Hanitsch LG, Meisel C, Kleint ME, Volk HD, et al. Altered B-cell subsets and functional B-cell defects in selective IgM deficiency. Clin Immunol. 2015;161:96–102.
Inoue T, Okumura Y, Shirama M, Ishibashi H, Kashiwagi S, Okubo H. Selective partial IgM deficiency: functional assessment of T and B lymphocytes in vitro. J Clin Immunol. 1986;6:130–5.
Ohno T, Inaba M, Kuribayashi K, Masuda T, Kanoh T, Uchino H. Selective IgM deficiency in adults: phenotypically and functionally altered profiles of peripheral blood lymphocytes. Clin Exp Immunol. 1987;68:630–7.
De la Concha EG, Garcia-Rodriguez MC, Zabay JM, Laso MT, Alonso F, Bootello A, et al. Functional assessment of T and B lymphocytes in patients with selective IgM deficiency. Clin Exp Immunol. 1982;49:670–6.
Goldstein MF, Goldstein AL, Dunsky EH, Dvorin DJ, Belecanech GA, Shamir K. Selective IgM immunodeficiency: retrospective analysis of 36 adult patients with review of the literature. Ann Allergy Asthma Immunol. 2006;97:717–30.
Hurez V, Kazatchkine MD, Vassilev T, Ramanathan S, Pashov A, Basuyaux B, et al. Pooled normal human polyspecific IgM contains neutralizing anti-idiotypes to IgG autoantibodies of autoimmune patients and protects from experimental autoimmune disease. Blood. 1997;90:4004–13.
Nguyen TT, Elsner RA, Baumgarth N. Natural IgM prevents autoimmunity by enforcing B cell central tolerance induction. J Immunol. 2015;194:1489–502.
Ehrenstein MR, Cook HT, Neuberger MS. Deficiency in serum immunoglobulin (Ig) M predisposes to development of IgG autoantibodies. J Exp Med. 2000;191:1253–8.
Boes M, Schmidt T, Linkemann K, Beaudette BC, Marshak-Rothstein A, Chen J. Accelerated development of IgG autoantibodies and autoimmune disease in the absence of secreted IgM. Proc Natl Acad Sci USA. 2000;97:1184–9.
Yel L, Ramanuja S, Gupta S. Clinical and immunological features in IgM deficiency. Int Arch Allergy Immunol. 2009;150:291–8.
Baumgarth N, Herman OC, Jager GC, Brown LE, Herzenberg LA, Chen J. B-1 and B-2 cell-derived immunoglobulin M antibodies are nonredundant components of the protective response to influenza virus infection. J Exp Med. 2000;192:271–80.
Subramaniam KS, Datta K, Quintero E, Manix C, Marks MS, Pirofski LA. The absence of serum IgM enhances the susceptibility of mice to pulmonary challenge with Cryptococcus neoformans. J Immunol. 2010;184:5755–67.
Guill MF, Brown DA, Ochs HD, Pyun KH, Moffitt JE. IgM deficiency: clinical spectrum and immunologic assessment. Ann Allergy. 1989;62:547–52.
Goldstein MF, Hilditch GJ, Dvorin DJ, Belecanech GA. Immunoglobulin replacement for selective IgM immunodeficiency, bronchiectasis, and asthma. Ann Allergy Asthma Immunol. 2016;116:172–3.
We would like to thank Editage (www.editage.com) for English editing.
Conflict of interest
The authors have declared that no conflict of interest exists.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee at which the studies were conducted (IRB approval number: H19-8908) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Shimamura, Y., Maeda, T., Abe, K. et al. Selective immunoglobulin M deficiency complicated by systemic lupus erythematosus and antiphospholipid syndrome: a case report and review of literature. CEN Case Rep (2021). https://doi.org/10.1007/s13730-021-00583-0
- Selective IgM deficiency
- Systemic lupus erythematosus
- Antiphospholipid syndrome