ANTIBODY DEFICIENCY AND AUTOIMMUNITY IN 22q11.2 DELETION SYNDROME

Gennery A, Barge D, O’Sullivan J, et al. Arch Dis Child. 2002;86:422–425 Purpose of the Study. The aim of this study was to investigate humoral immunity, particularly antibody response to pneumococcal polysaccharide, and autoimmune anomalies in a cohort of patients with 22q11 deletion. Study Population. Thirty-two patients from the Newcastle, United Kingdom (UK) Pediatric Immunology Clinic were identified based on referrals for the diagnosis of 22q11 deletion or because a patient with 22q11 deletion was suffering from recurrent infections. Methods. A history of severe or recurrent bacterial infection and autoimmune symptoms were noted. Lymphocyte subsets, immunoglobulins, immunoglobulin G (IgG) subclasses, specific vaccine antibodies, and autoantibodies were measured. Subjects were vaccinated with appropriate antigens when specific antibodies were low. Results. Twenty-six (81%) of the 32 patients had severe or recurrent infections, of which 13 (50%) had abnormal serum immunoglobulin levels and 11 of 20 (55%) 4 years old had an abnormal antibody response to pneumococcal polysaccharide antigen. Ten of 30 (33%) patients investigated had autoimmune phenomena, of which 6 were symptomatic, and all 10 had either low immunoglobulins or poor response to specific vaccine antigens. Conclusions. Humoral immunodeficiency appears to be more common than has been previously recognized. Normal T cell function and normal immunoglobulin levels do not exclude poor specific antibody responses and susceptibility to severe or recurrent bacterial infections. Patients diagnosed with 22q11 deletion should be referred for formal investigation of both cellular and humoral immune function, including response to conjugated pneumococcal vaccines. Reviewers’ Comments. This study adds important information to our knowledge of the potential immune dysfunction in patients with 22q11 deletion. The exact mechanisms of the abnormalities in humoral immunity and the high incidence of autoimmune phenomena remain unclear and need to be determined. Although the authors state that there is reporting bias in the study based on whether patients were referred simply on the basis of their diagnosis or because of recurrent infections, they did not state how many patients were identified by which type of referral. Furthermore, there is likely more bias because this referral center may evaluate the most severe cases in the area. This study only involves a small group of patients from 1 center, and thus additional studies involving multicenter and multinational cohorts are necessary to see if the reported abnormalities occur as frequently.