Defective activation of the alternative pathway of complement in two brothers with ataxia-telangiectasia

Two brothers with ataxia-telangiectasia and recurrent respiratory tract infections are presented. Immunological investigations showed normal immunoglobulin levels (except for the absence of IgA in one child) with absence of haemagglutination inhibiting antibody response to inactivated influenza virus vaccine, normal total lymphocyte counts with decreased T cell numbers, absence of delayed hypersensitivity skin reaction to PPD, in vitro unresponsiveness of T lymphocytes to PHA with presence of a serum inhibitor able to depress normal lymphocyte transformation, and normal phagocytosis and killing of Staph. aureus by peripheral blood polymorphonuclear leucocytes. Complete complement screening revealed a non-functioning alternative pathway in both brothers. The presence of normal factor B lytic activity after isoelectrofocusing the serum and inhibition of the lytic activity of purified components with the patients' serum raised the possibility of a serum inhibitor. The nature of this was not elucidated but it may be one of the reasons why patients with ataxia-telangiectasia have an increased incidence of infections.