Regulation of peripheral blood B-cell IgA production in alcoholic cirrhosis.
In alcoholic cirrhosis, high levels of serum IgA make a prominent contribution to hyperglobulinaemia. Kinetic studies indicate that this predominantly reflects enhanced IgA synthesis rather than catabolism. Increase IgA synthesis might reflect increased antigenic load, diminished T-cell suppression, or T-cell independent B-cell stimulation (for example by lipopolysaccharide). To investigate this we studied T-cell control of IgA production by peripheral blood cells. Six patients with alcoholic cirrhosis were compared with six normal individuals. Serum IgA levels were significantly higher in the patients (6.6 mg/ml, SD 2.8 cf 1.7 mg/ml, SD 1.2). Seven day unstimulated cultures of peripheral blood mononuclear cells yielded supernatant IgA concentrations of 1,025 ng/ml (SD 600) in patients and 363 ng/ml (SD 222) in controls. T-cell control of IgA synthesis was explored by rosetting out T-cells, and reconstituting cultures at varying T:non-T cell ratios. Similarly shaped curves relating IgA per million non-T cells to the T:non-T cell ratio were found, with maximum IgA production at a T:non-T ratio of 8:2 in each group. IgA production at this ratio was 6.4 micrograms/ml/million non-T cells (SD 3.2) in cirrhosis of 3.2 (SD 1.0) in controls. T-cell control of IgA production thus appears normal, though set at a higher level, implying enhanced T-cell independent drive to IgA production in alcoholic cirrhosis.
Allison
M E
ME
Gastroenterology Unit, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
Hodgson
H J
HJ
D001402:B-Lymphocytes / Q000276:immunology*; D005786:Gene Expression Regulation; D006801:Humans; D006942:Hypergammaglobulinemia / Q000209:etiology*; D007070:Immunoglobulin A / Q000096:biosynthesis*; D007958:Leukocyte Count; D008104:Liver Cirrhosis, Alcoholic / Q000150:complications / Q000276:immunology*; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
D007070:Immunoglobulin A