Journal Article

Clinical features of patients with homozygous complement C4A or C4B deficiency

Järvinen, Asko, Valtonen, Ville, Paakkanen, Riitta, Liesmaa, Inka, Lokki, Marja-Liisa

2018

Overview

Homozygous deficiencies of complement C4A or C4B are detected in 1-10% of populations. In genome-wide association studies C4 deficiencies are missed because the genetic variation of C4 is complex. There are no studies where the clinical presentation of these patients is analyzed. This study was aimed to characterize the clinical features of patients with homozygous C4A or C4B deficiency. Thirty-two patients with no functional C4A, 87 patients with no C4B and 120 with normal amount of C4 genes were included. C4A and C4B numbers were assessed with genomic quantitative real-time PCR. Medical history was studied retrospectively from patients' files. Novel associations between homozygous C4A deficiency and lymphoma, coeliac disease and sarcoidosis were detected. These conditions were present in 12.5%, (4/32 in patients vs. 0.8%, 1/120, in controls, OR = 17.00, 95%CI = 1.83-158.04, p = 0.007), 12.5% (4/32 in patients vs. 0%, 0/120 in controls, OR = 1.14, 95%CI = 1.00-1.30, p = 0.002) and 12.5%, respectively (4/32 in patients vs. 2.5%, 3/120 in controls, OR = 5.571, 95%CI = 1.79-2.32, p = 0.036). In addition, C4A and C4B deficiencies were both associated with adverse drug reactions leading to drug discontinuation (34.4%, 11/32 in C4A-deficient patients vs. 14.2%, 17/120 in controls, OR = 3.174, 95%CI = 1.30-7.74, p = 0.009 and 28.7%, 25/87 in C4B-deficient patients, OR = 2.44, 95%CI = 1.22-4.88, p = 0.010). This reported cohort of homozygous deficiencies of C4A or C4B suggests that C4 deficiencies may have various unrecorded disease associations. C4 gene should be considered as a candidate gene in studying these selected disease associations.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adult / Analysis / Asthma / Autoimmune diseases / Autoimmunity - genetics / Biology and Life Sciences / Cardiovascular disease / Celiac disease / Chromosomes / Complement C4a - deficiency / Complement C4a - genetics / Complement C4b - deficiency / Complement C4b - genetics / Complement component C4 / Complement system / Drug-Related Side Effects and Adverse Reactions - immunology / Family medical history / Female / Genes / Genetic aspects / Genetic diversity / Genome-wide association studies / Genomes / Homozygote / Hospitals / Humans / Infections / Infectious diseases / Inflammation / Ischemia / Laboratories / Lectins / Lupus / Lymphoma / Male / Medicine and Health Sciences / Middle Aged / Patients / Population studies / Rheumatoid arthritis / Sarcoidosis / Side effects / Tuberculosis