Hyper IgG3/IgA2 syndrome: Gene deletion or IgG subclass regulatory defect?

Academic Article

Abstract

  • IgG and IgA are divided into subclasses which are encoded by heavy chain constant region genes on chromosome 14 in the order γ3, γ1, α1, γ2, γ4, ε, and α2. The mechanism of subclass switching is not entirely defined although naturally occurring deletions and isotype switching deficiencies may be informative. The description and investigation of this patient with abnormal immunogtobulin levels may provide information concerning these mechanisms. The patient is a 42 year old white male who presented for evaluation of recurrent sinusitis (4-5 infections/year). No family history of recurrent or fatal infections was obtained. The physical examination was normal. The patient's serum IgG was 520 mg/dl (620-1400 mg/dl), IgA was 317 mg/dl (75-375 mg/dl), IgM was 216 mg/dl (33-232 mg/dl) and IgE was 158 IU/ml. IgG1 was<1 mg/dl (450-1400 mg/dl), IgG2 was <1 mg/dl (100-700 mg/dl), IgG3 was 522 mg/dl (35-160 mg/dl) and IgG4 was <1 mg/dl (1-150 mg/dl). Serum IgA1 was <1 mg/dl and IgA2 was 310 mg/dl. Antibodies to Hemophilus influenza B, Diphtheria, and post vaccination titers to Pneumovax were diminished to absent and those present were IgG3. Antibodies to tetanus were normal and were IgG3. The peripheral blood lymphocytes were within normal range; (CD3+ T cells were 1,520 (710-4, 180 × 109/L; CD3+CD4+ T cells were 1,100 (350-2740 × 109/L; CD3+ CD8+ T cells were 400 (80-1, 490 × 109/L); CD19+ B cells were 230 (70-910 × 109/L; CD16+NK cells were 340 (0-860 × 109/L)). The genes encoding the absent serum immunoglobulins of this patient are sequentially located in the heavy chain locus. Studies are under way to determine if the abnormalities found are the result of a gene deletion or a regulatory defect.
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    Volume

  • 12
  • Issue

  • 5