Association of autoimmunity with IgG2 and IgG4 subclass deficiency in a growth hormone-deficient child

An association between humoral immune deficiency and childhood autoimmune disease has been previously established. We describe a 7-year-old male with severe autoimmune disease, recurrent infections, a marked deficiency of IgG2 and IgG4, and an inability to respond to polysaccharide antigens. This child was also found to have isolated growth hormone (GH) deficiency. Laboratory results included a positive anti-smooth muscle antibody, a positive Raji-cell assay for immune complexes, and normal levels of IgG, IgM, and IgA. IgG subclasses revealed an IgG1 of 1225 (normal for age, 280-1120 mg/dl), IgG2 of less than 10 (30-630 mg/dl), IgG3 of 36 (40-250 mg/dl), and IgG4 of less than 4 (11-620 mg/dl). No increase in antibody titer was noted to either Pneumovax or unconjugated Haemophilus influenzae vaccine. Numbers of circulating B cells (CD19) were markedly diminished (less than 0.5%). Liver biopsies have shown chronic active hepatitis. Somatomedin C was 0.28 U/ml (normal for age, 0.5-2.06 U/ml). Challenge with either L-dopa or clonidine produced a peak GH response of 2.3 ng/ml (normals = greater than 7 ng/ml). Children with autoimmune disorders should be evaluated for IgG subclass deficiencies and ability to make antibody in response to antigen challenge regardless of the serum immunoglobulin levels. Growth failure in immune-deficient children should not be assumed to be due to chronic illness or recurrent infections. Other etiologies for growth failure should be sought.