Characterization of Patients With an Increased Susceptibility to Bacterial Infections and a Genetic Deficiency of Leukocyte Membrane Complement Receptor Type 3 and the Related Membrane Antigen LFA

Three children from two unrelated families had a history of recurrent bacterial infections, and their neutrophils were shown to have deficient phagocytic and respiratory responses and possible deficiencies in chemotaxis or adherence. Their neutrophils were strikingly deficient in the ability to ingest or give a respiratory burst in response to unopsonized bakers’ yeast or zymosan (Z). Tests for neutrophil and monocyte CR1 (C3b/iC3b receptor) and CR3 (iC3b receptor) demonstrated rosettes with both EC3b and EC3bi. However, EC3bi were bound only to CR1, and not to CR3. because EC3bi rosettes were inhibited completely by anti-CR1. Neutrophils. monocytes. and natural killer (NK) cells also did not fluorescence stain with monoclonal antibodies specific for the a-chain of CR3 (anti-Mac-i , antiMol, OKM1 . and MN-41 ). Quantitation of C receptors with 1251 monoclonal anti-CR1 and anti-CR3 indicated that neutrophils from each patient expressed normal amounts of CR1 per cell but <10% of the normal amount of CR3. Examination of neutrophils by sodium dodecyl sulfate-polyacrylamide gel electrophoresis demonstrated that a normal glycoprotein of -165,000 daltons was missing. Immunoblotting of these gels indicated that the missing band was