A "spontaneous" cold-reactive IgM antibody with anti HLA-B8 specificity in a patient with multiple sclerosis

A case of a 35-year-old female with multiple sclerosis is reported who developed without apparent prior sensitization a lymphocytotoxic antibody with anti-HLA-B8 specificity. The antibody persisted for several years with the same titer. The cytotoxic activity of the patient's serum was contained within the IgM fraction. The antibody reacted optimally at low temperature, exclusively against lymphocytes homozygous for HLA-B8. In B8-heterozygous cells, cytotoxic reactions were obtained only following enzymatic pretreatment. The antibody's binding avidity was weak; for its complete absorption, many times more B8-positive lymphocytes or platelets were needed than for a "normal" anti-B8 antibody of the same titer. In HLA redistribution and blocking experiments, it was demonstrated that the antigenic determinant recognized by this antibody is carried by the B8 molecule. It is unclear whether "spontaneously" occurring cold-reactive IgM antibodies with HLA specificity are induced by viral agents or whether they reflect "spontaneous" clonal lymphocyte proliferation.