HIV-Negative Brother and Sister with Decreased CD4/CD8 Ratios and Different-Type Nephritides

Toshio Murakami, MD, Department of Pediatrics, Yamaguchi University School of Medicine, 1144Kogushi, Ube, Yamaguchi 755 (Japan) Dear Sir, We describe here 2 HIV-negative siblings with decreased CD4/CD8 ratios and renal disease. The parents were unrelated. The brother, at age 1 year and 9 months, suffered from transient agranulocytosis. Serum IgG, IgA, and IgM were elevated at 1,270, 156, and 127 mg/dl, respectively. At age 1 year and 11 months, a microscopic hematuria was noted at which time serum IgG and IgA were still elevated, while serum IgM was 31 mg/dl. At age 4, streptococcal pharyngitis temporarily worsened the urinary finding. One month later, we noticed petechiae on his abdomen. The diagnosis of idiopathic thrombocytopenic purpura was made. Coin-cidentally, he showed a selective IgM deficiency. Serum complements were normal. No autoantibodies to nuclei, lymphocytes or DNA were detectable. Serum immune complexes were detected transiently. Thrombo-cytopenia was improved with oral prednisolone and serum IgM rose to 40 mg/dl. He normally had IgM isohemagglutinin to B group substances. Renal biopsy performed when he was on 20 mg/day prednisolone, revealed stage I membranous nephropathy with granular deposition of IgG (2+), IgA (1+), Clq (3+), C3 (2+), and C4 (1+) along the glomerular basement membrane, but not IgM. The microscopic hematuria continued even after the disappearance of proteinuria. Lymphocyte subsets are shown in table 1. B-cell subpopulations were within the normal or nearly normal range. Lymphocytes were poorly transformed by either PHA or Con A, and the activity of ADCC was decreased, despite being on 30 mg/day prednisolone. He had no antibody to either HIV-1 or HTLV-1. At age 4 years and 6 months, whilst on 15 mg prednisolone every other day, he developed fever and swelling of the axillar lymph nodes. Neither cervical nor inguinal lymph nodes were involved. He showed pan-cytopenia and hypercellular bone marrow (M/E ratio, 6.24). Serum IgM was 15 mg/dl, but IgG and IgA were still elevated. Serum ß2-microglobulin was increased at 3,950 ng/ ml. Antilymphocyte antibody was detected transiently.