Multiple Types of Autoimmunity Resulting from the same CD40 Ligand Mutation

Document Type : Original Article

Author

Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children Medical Center, Tehran University of Medical Science, Tehran, Iran

Abstract

Abstract:
Background/Objectives: Hyper-immunoglobulin M (HIgM) syndrome is a primary immunodeficiency disease in which impaired immunoglobulin class-switch recombination causes normal or high levels of serum IgM versus low or undetectable serum levels of class-switched immunoglobulins.
Methods: The diagnoses of all patients with HIgM in familial cases were evaluated based on genetic testing. Since this syndrome can present with either infectious diseases, malignancies, or autoimmune diseases, all medical complications were recorded in the index patients and relatives.
Results: Surprisingly, the evaluation identified a family with 3 males suffering from CD40 ligand deficiency, and each one had different autoimmune manifestations, including Guillain-barre syndrome and pauciarticular and polyarticular juvenile rheumatoid arthritis.
Conclusions: Based on the results, it is hypothesized that other genetic modifying factors or environmental parameters affecting epigenetics may have a significant role in the presentation of autoimmunity in CD40 ligand deficiency.

Keywords


1.         Levy J, Espanol-Boren T, Thomas C, Fischer A, Tovo P, Bordigoni P, et al. Clinical spectrum of X-linked hyper-IgM syndrome. J Pediatr. 1997;131(1 Pt 1):47-54.
2.         Schimke RN, Bolano C, Kirkpatrick CH. Immunologic deficiency in the congenital rubella syndrome. Am J Dis Child. 1969;118(4):626-33.
3.         Raziuddin S, Assaf HM, Teklu B. T cell malignancy in Richter's syndrome presenting as hyper IgM. Induction and characterization of a novel CD3+, CD4-, CD8+ T cell subset from phytohemagglutinin-stimulated patient's CD3+, CD4+, CD8+ leukemic T cells. Eur J Immunol. 1989;19(3):469-74.
4.         Mitsuya H, Tomino S, Hisamitsu S, Kishimoto S. Evidence for the failure of IgA specific T helper activity in a patient with immunodeficiency with hyper IgM. J Clin Lab Immunol. 1979;2(4):337-42.
5.         Espanol T, Canals C, Bofill A, Moreno A, Sentis M. Immunological abnormalities in late onset rubella syndrome and correction with gammaglobulin treatment. Progress in Immunodeficiency Research and Therapy II. 1986:401.
6.         Gordon J, Millsum MJ, Guy GR, Ledbetter JA. Resting B lymphocytes can be triggered directly through the CDw40 (Bp50) antigen. A comparison with IL-4-mediated signaling. J Immunol. 1988;140(5):1425-30.
7.         Benkerrou M, Gougeon ML, Griscelli C, Fischer A. [Hypogammaglobulinemia G and A with hypergammaglobulinemia M. Apropos of 12 cases]. Arch Fr Pediatr. 1990;47(5):345-9.
8.         Brahmi Z, Lazarus KH, Hodes ME, Baehner RL. Immunologic studies of three family members with the immunodeficiency with hyper-IgM syndrome. J Clin Immunol. 1983;3(2):127-34.
9.         Beall GN, Ashman RF, Miller ME, Easwaran C, Raghunathan R, Louie J, et al. Hypogammaglobulinemia in mother and son. J Allergy Clin Immunol. 1980;65(6):471-81.
10.       Jesus AA, Duarte AJ, Oliveira JB. Autoimmunity in hyper-IgM syndrome. J Clin Immunol. 2008;28 Suppl 1:S62-6.
11.       Hollenbaugh D, Wu LH, Ochs HD, Nonoyama S, Grosmaire LS, Ledbetter JA, et al. The random inactivation of the X chromosome carrying the defective gene responsible for X-linked hyper IgM syndrome (X-HIM) in female carriers of HIGM1. J Clin Invest. 1994;94(2):616-22.
12.       Filipovich AH, Mathur A, Kamat D, Kersey JH, Shapiro RS. Lymphoproliferative disorders and other tumors complicating immunodeficiencies. Immunodeficiency. 1994;5(2):91-112.
13.       Seyama K, Nonoyama S, Gangsaas I, Hollenbaugh D, Pabst HF, Aruffo A, et al. Mutations of the CD40 ligand gene and its effect on CD40 ligand expression in patients with X-linked hyper IgM syndrome. Blood. 1998;92(7):2421-34.
14.       Hayward AR, Levy J, Facchetti F, Notarangelo L, Ochs HD, Etzioni A, et al. Cholangiopathy and tumors of the pancreas, liver, and biliary tree in boys with X-linked immunodeficiency with hyper-IgM. J Immunol. 1997;158(2):977-83.
15.       Rochman Y, Kashyap M, Robinson GW, Sakamoto K, Gomez-Rodriguez J, Wagner KU, et al. Thymic stromal lymphopoietin-mediated STAT5 phosphorylation via kinases JAK1 and JAK2 reveals a key difference from IL-7-induced signaling. Proc Natl Acad Sci U S A. 2010;107(45):19455-60.
16.       Fang M, Abolhassani H, Lim CK, Zhang J, Hammarstrom L. Next Generation Sequencing Data Analysis in Primary Immunodeficiency Disorders - Future Directions. J Clin Immunol. 2016;36 Suppl 1:68-75.
17.       Li R, Yu C, Li Y, Lam TW, Yiu SM, Kristiansen K, et al. SOAP2: an improved ultrafast tool for short read alignment. Bioinformatics. 2009;25(15):1966-7.
18.       Li R, Li Y, Fang X, Yang H, Wang J, Kristiansen K, et al. SNP detection for massively parallel whole-genome resequencing. Genome Res. 2009;19(6):1124-32.
19.       McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K, Kernytsky A, et al. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 2010;20(9):1297-303.
20.       Li H, Durbin R. Fast and accurate long-read alignment with Burrows-Wheeler transform. Bioinformatics. 2010;26(5):589-95.
21.       Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405-24.
22.       Notarangelo LD, Duse M, Ugazio AG. Immunodeficiency with hyper-IgM (HIM). Immunodefic Rev. 1992;3(2):101-21.
23.       Webster EA, Khakoo AY, Mackus WJ, Karpusas M, Thomas DW, Davidson A, et al. An aggressive form of polyarticular arthritis in a man with CD154 mutation (X-linked hyper-IgM syndrome). Arthritis Rheum. 1999;42(6):1291-6.
24.       Sordet C, Cantagrel A, Schaeverbeke T, Sibilia J. Bone and joint disease associated with primary immune deficiencies. Joint Bone Spine. 2005;72(6):503-14.
25.       Sibilia J, Durandy A, Schaeverbeke T, Fermand JP. Hyper-IgM syndrome associated with rheumatoid arthritis: report of RA in a patient with primary impaired CD40 pathway. Br J Rheumatol. 1996;35(3):282-4.
26.       Potocnik AJ, Kinne R, Menninger H, Zacher J, Emmrich F, Kroczek RA. Expression of activation antigens on T cells in rheumatoid arthritis patients. Scand J Immunol. 1990;31(2):213-24.
27.       Kraakman ME, de Weers M, Espanol T, Schuurman RK, Hendriks RW. Identification of a CD40L gene mutation and genetic counselling in a family with immunodeficiency with hyperimmunoglobulinemia M. Clin Genet. 1995;48(1):46-8.
28.       Sakaguchi N, Takahashi T, Hata H, Nomura T, Tagami T, Yamazaki S, et al. Altered thymic T-cell selection due to a mutation of the ZAP-70 gene causes autoimmune arthritis in mice. Nature. 2003;426(6965):454-60.
29.       Tsokos GC, Smith PL, Balow JE. Development of hypogammaglobulinemia in a patient with systemic lupus erythematosus. Am J Med. 1986;81(6):1081-4.
30.       Sany J, Jorgensen CH, Anaya JM, Didry C, Andary M, Serre I, et al. Arthritis associated with primary agammaglobulinemia: new clues to its immunopathology. Clin Exp Rheumatol. 1993;11(1):65-9.
31.       Chattopadhyay C, Natvig JB, Chattopadhyay H. Excessive suppressor T-cell activity of the rheumatoid synovial tissue in X-linked hypogammaglobulinaemia. Scand J Immunol. 1980;11(4):455-9.
32.       Teller K, Budhai L, Zhang M, Haramati N, Keiser HD, Davidson A. HLA-DRB1 and DQB typing of Hispanic American patients with rheumatoid arthritis: the "shared epitope" hypothesis may not apply. J Rheumatol. 1996;23(8):1363-8.
33.       Rathmell JC, Townsend SE, Xu JC, Flavell RA, Goodnow CC. Expansion or elimination of B cells in vivo: dual roles for CD40- and Fas (CD95)-ligands modulated by the B cell antigen receptor. Cell. 1996;87(2):319-29.
34.       Herve M, Isnardi I, Ng YS, Bussel JB, Ochs HD, Cunningham-Rundles C, et al. CD40 ligand and MHC class II expression are essential for human peripheral B cell tolerance. J Exp Med. 2007;204(7):1583-93.
35.       Thien M, Phan TG, Gardam S, Amesbury M, Basten A, Mackay F, et al. Excess BAFF rescues self-reactive B cells from peripheral deletion and allows them to enter forbidden follicular and marginal zone niches. Immunity. 2004;20(6):785-98.
36.       Mackay F, Woodcock SA, Lawton P, Ambrose C, Baetscher M, Schneider P, et al. Mice transgenic for BAFF develop lymphocytic disorders along with autoimmune manifestations. J Exp Med. 1999;190(11):1697-710.
37.       Lacroix-Desmazes S, Resnick I, Stahl D, Mouthon L, Espanol T, Levy J, et al. Defective self-reactive antibody repertoire of serum IgM in patients with hyper-IgM syndrome. J Immunol. 1999;162(9):5601-8.
38.       Kumanogoh A, Wang X, Lee I, Watanabe C, Kamanaka M, Shi W, et al. Increased T cell autoreactivity in the absence of CD40-CD40 ligand interactions: a role of CD40 in regulatory T cell development. J Immunol. 2001;166(1):353-60.
39.       Stout RD, Suttles J. The many roles of CD40 in cell-mediated inflammatory responses. Immunol Today. 1996;17(10):487-92.
40.       DiPalma JA, Strobel CT, Farrow JG. Primary sclerosing cholangitis associated with hyperimmunoglobulin M immunodeficiency (dysgammaglobulinemia). Gastroenterology. 1986;91(2):464-8.
41.       Stephens J, Cosyns M, Jones M, Hayward A. Liver and bile duct pathology following Cryptosporidium parvum infection of immunodeficient mice. Hepatology. 1999;30(1):27-35.
42.       Rosen FS, Cooper MD, Wedgwood RJ. The primary immunodeficiencies. N Engl J Med. 1995;333(7):431-40.
43.       Roberts-Thomson PJ, Shepherd K. Low molecular weight IgM in primary biliary cirrhosis. Gut. 1990;31(1):88-91.
44.       Poupon R, Chazouilleres O, Balkau B, Poupon RE. Clinical and biochemical expression of the histopathological lesions of primary biliary cirrhosis. UDCA-PBC Group. J Hepatol. 1999;30(3):408-12.
45.       Gershwin ME, Ansari AA, Mackay IR, Nakanuma Y, Nishio A, Rowley MJ, et al. Primary biliary cirrhosis: an orchestrated immune response against epithelial cells. Immunol Rev. 2000;174:210-25.
46.       Ishibashi H, Nakamura M, Shimoda S, Gershwin ME. T cell immunity and primary biliary cirrhosis. Autoimmun Rev. 2003;2(1):19-24.
47.       Selmi C, Gershwin ME. Bacteria and human autoimmunity: the case of primary biliary cirrhosis. Curr Opin Rheumatol. 2004;16(4):406-10.
48.       Bogdanos DP, Baum H, Grasso A, Okamoto M, Butler P, Ma Y, et al. Microbial mimics are major targets of crossreactivity with human pyruvate dehydrogenase in primary biliary cirrhosis. J Hepatol. 2004;40(1):31-9.
49.       Villa A, Notarangelo LD, Di Santo JP, Macchi PP, Strina D, Frattini A, et al. Organization of the human CD40L gene: implications for molecular defects in X chromosome-linked hyper-IgM syndrome and prenatal diagnosis. Proc Natl Acad Sci U S A. 1994;91(6):2110-4.
50.       Aghamohammadi A, Parvaneh N, Rezaei N, Moazzami K, Kashef S, Abolhassani H, et al. Clinical and laboratory findings in hyper-IgM syndrome with novel CD40L and AICDA mutations. J Clin Immunol. 2009;29(6):769-76.
51.       Wood P, Stanworth S, Burton J, Jones A, Peckham DG, Green T, et al. Recognition, clinical diagnosis and management of patients with primary antibody deficiencies: a systematic review. Clin Exp Immunol. 2007;149(3):410-23.
52.       Giralt S, Estey E, Albitar M, van Besien K, Rondon G, Anderlini P, et al. Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft-versus-leukemia without myeloablative therapy. Blood. 1997;89(12):4531-6.
53.       Gennery AR, Khawaja K, Veys P, Bredius RG, Notarangelo LD, Mazzolari E, et al. Treatment of CD40 ligand deficiency by hematopoietic stem cell transplantation: a survey of the European experience, 1993-2002. Blood. 2004;103(3):1152-7.