Hiperimmünglobulin M Sendromu Tanısı Alan Vakaların Klinik ve Laboratuvar Özelliklerinin Değerlendirilmesi

Abstract

Akarsu A, Clinical and laboratory features of patients with Hyperimmunoglobulin M syndrome, Hacettepe University Faculty of Medicine, Thesis in Pediatrics, Ankara, 2017. Primer immunodeficiencies are a group of diseases that occur as a result of disorders in the development, differentiation or function of cells and components in the immune system, predisposing to conditions such as infections, autoimmunity, allergy, inflammation and malignancy. Primer immunodeficiencies are rare diseases in western countries, but autosomal recessively inherited forms are frequently observed in countries where consanguineous marriages are frequent. Patients with hyperimmunoglobulin M syndrome have predisposition to autoimmune diseases and infections due to immunodeficiency resulting from isotype switching and/ or somatic hypermutation mechanism. The aim of our study is to investigate the correlation of clinical and laboratory parameters with the genetic mutations defined in patients. 49 patients who had been diagnosed with clinical and laboratory values as hyperimmunoglobulin M syndrome between June 1985 and June 2017 in the Department of Immunology at İhsan Doğramacı Children's Hospital of Hacettepe University were included this study. 18 patients have AID defects, 13 patients have CD40L defect, 2 patients have CD40 defect, one patient has HIGM type 4, and 3 patients have other defects (ATM gene mutation, Artemis gene mutation and Cernunnos gene defect). At the time of admission, the median IgG value was 130 mg/dL (17-718), IgM value was 483 mg/dL (30-8720) and IgA value was 21mg/dL (6.06-404). IgM levels were higher than the normal range in 63% of the patients, 30.4% in the normal range and 6.5% in lower than the normal range. The complaints of the patients were frequent infections (69.4%), severe infections (16.3%) and admission related to siblings with similar illnesses (14.3%). The most common infection was pneumonia. Candida subtypes and H. influenza were the most common microorganisms that could be isolated as agents for pneumonia. Other common infections in the patients were diarrhea, ear infection, sinusitis and recurrent upper respiratory tract infection. Non-infectious complications were seen in 54.2% (26 patients) of the patients. The most common non-infectious finding was arthritis. Eosinophilia is the most common hematologic disorder. Also neutropenia, thrombocytopenia and lymphopenia were observed in patients. All patients were given intravenous immunoglobulin therapy, hematopoietic stem cell transplantation was performed in 1 patient, and stem cell transplantation was planned in 2 patients. During the follow-up period, 10 cases died because of infectious, autoimmune and malignant causes. It has been observed that eosinophilia is an important finding in our patients and rheumatic findings may be one of the manifestation of HIGM syndrome. IgM levels in the patients with CD40L deficiency were lower than the normal range, suggesting that the diagnostic criteria of the disease should be reevaluated.