Common variable immunodeficiency 8 D81.4

Variable immunodeficiency syndrome 8 with autoimmunity and mutation in the LRBA gene is a phenotypically heterogeneous, autosomal recessive inherited disorder of immune regulation. It is associated with mutations in the LRBA gene located on chromosome 4q31.3.

Affected individuals have recurrent infections in early childhood, particularly respiratory infections, and develop variable autoimmune diseases, including idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia, and inflammatory bowel disease. Less common are inflammatory exanthema (reviewed by Lopez-Herrera et al. 2012; Alangari et al. 2012).

Immunologic findings are variable; possible findings include decreased B cells, hypogammaglobulinemia, decreased CD4+ T regulatory (Treg) cells (Charbonnier et al. 2015).

Lopez-Herrera et al (2012) reported on five patients from four unrelated blood families who developed humoral immunodeficiency and autoimmunity in early infancy. Two siblings were diagnosed with idiopathic thrombocytopenic purpura (ITP) in infancy, recurrent respiratory infections, and otitis media. Both developed chronic lung disease and bronchiectasis. Laboratory tests revealed low immunoglobulin levels suggestive of a CVID diagnosis. A Sicilian boy presented at 12 years of age with recurrent warts and perineal molluscum contagiosum. He later developed recurrent severe respiratory infections with interstitial pneumonitis and bronchiectasis, idiopathic thrombocytopenic purpura , autoimmune hemolytic anemia, atrophic gastritis due to autoantibodies to intrinsic factor, a submaxillary abscess, and colitis. Laboratory tests revealed low IgG and complete IgA deficiency with normal neutrophil count. Biopsies of the hilar and mediastinal lymph nodes showed lymphoid follicular hyperplasia with absence of the follicular mantle zone. He also developed a brain tumor in the right temporal lobe, which proved to be a granulomatous infiltration with T cells, plasma cells, and macrophages but few B cells. Another patient, who died at 19 years of age, suffered from recurrent diarrhea, recurrent upper respiratory tract infections, hypothyroidism, myasthenia gravis, and allergic dermatitis.

Alangari et al (2012) reported 5 patients with an inherited disorder of immune regulation. One branch of the family included 3 sisters aged 15 to 22 years. Two of the sisters presented with chronic nonbloody diarrhea in the early years of life, whereas the third sister suffered from recurrent respiratory infections since the age of 4 and developed diarrhea at the age of 18. Colon biopsies from 2 patients showed mucosal inflammation and lymphocytic infiltration, and duodenal biopsy from 1 patient showed villous atrophy. One sister developed autoimmune thrombocytopenia and autoimmune hemolytic anemia. Lab: Low serum IgA and IgG levels with normal numbers of T and NK cells but markedly decreased proliferative T-cell responses. Two of the sisters had decreased numbers of B cells.

Two siblings from the other branch of the family presented with chronic diarrhea in childhood. Duodenal biopsies showed villous atrophy and lymphocytic infiltration. One patient developed pancytopenia that responded to IVIG and steroids; he also had Epstein-Barr virus (EBV)-induced lymphoproliferative disease. None of the siblings had a history of recurrent infections, and immunologic examination revealed normal Ig levels; normal B, T, and NK cells; normal T-cell proliferative responses; and normal antibody production in response to vaccination.

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