Abstract
Complement deficiencies are rare and often underdiagnosed primary immunodeficiencies that may be associated with invasive bacterial diseases. Serious infections with encapsulated organisms (mainly Streptococcus pneumoniae, but also Neisseria meningitides and Haemophilus influenzae type B) are frequent in patients with a deficiency of the second component of complement (C2), but no data are available on long-term follow-up. This study aimed to evaluate the long-term clinical outcome and the importance of an early diagnosis and subsequent infection prophylaxis in C2 deficiency. Here, we report the 21-year follow-up of a whole family which was tested for complement parameters, genetic analysis and biochemical measurements, due to recurrent pneumococcal meningitis in the elder brother. The two sons were diagnosed with homozygous type 1 C2 deficiency, while their parents were heterozygous with normal complement parameters. For the two brothers, a recommended vaccination program and antibiotic prophylaxis were prescribed. During the long-term follow-up, no severe/invasive infections were observed in either patient. At the age of 16, the younger brother developed progressive hypogammaglobulinemia of all three classes, IgA, IgM and IgG. A next generation sequencing panel excluded the presence of gene defects related to primary antibody deficiencies. Our data show that early diagnosis, use of vaccinations and antibiotic prophylaxis may allow a normal life in hereditary C2 deficiency, which can be characterized using functional and genetic methods. Moreover, a periodical check of immunoglobulin serum levels could be useful to detect a possible hypogammaglobulinemia.
Highlights
The complement is a multi-functional complex system of the innate immunity comprising more than 30 proteins which are produced mainly by the liver and consist of activators and inhibitors interacting with each other to form three pathways of activation [1,2,3].Medicina 2020, 56, 120; doi:10.3390/medicina56030120 www.mdpi.com/journal/medicinaThis system has an important role in host defense against infectious agents, in the removal of apoptotic cells and immune complexes, and in the modulation of the adaptive immune system [2]
This study, in which we report the case and the 21-year follow-up of two brothers diagnosed with homozygous type 1 C2 deficiency and of their parents, shows that early diagnosis, use of vaccinations and antibiotic prophylaxis may allow a normal life in hereditary C2 deficiency
The frequency of congenital complement deficiency has been calculated to be about 0.03% in Western countries and Japan, excluding mannose binding lectin (MBL) deficiency, which has been estimated to occur in its recessive form in about 5% of the population [7,12,21]
Summary
This system has an important role in host defense against infectious agents, in the removal of apoptotic cells and immune complexes, and in the modulation of the adaptive immune system [2]. Bacterial infections and autoimmune diseases are clinical conditions most frequently associated with complement defects [2]. Homozygous hereditary deficiency of each of the early proteins of the classical pathway of complement activation is strongly associated with the development of autoimmune diseases. The deficiency of the second complement component (C2) is associated with a low prevalence of SLE, estimated at approximately 10% [2,5]
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