Division of Infectious Diseases, Inflammation Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Transplantation Laboratory, Medicum, University of Helsinki, Helsinki, Finland.
PLoS One. 2018 Jun 21;13(6):e0199305. doi: 10.1371/journal.pone.0199305. eCollection 2018.
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.
在 1%至 10%的人群中可检测到补体 C4A 或 C4B 的纯合子缺失。在全基因组关联研究中，由于 C4 的遗传变异复杂，C4 缺乏症会被遗漏。目前还没有研究分析这些患者的临床表现。本研究旨在描述纯合子 C4A 或 C4B 缺乏症患者的临床特征。
共纳入 32 例无功能性 C4A 患者、87 例无 C4B 患者和 120 例 C4 基因正常量患者。采用基因组实时定量 PCR 评估 C4A 和 C4B 的数量。从患者病历中回顾性研究病史。
发现纯合子 C4A 缺乏与淋巴瘤、乳糜泻和结节病之间存在新的关联。这些疾病在患者中的发生率为 12.5%（4/32 例 vs. 0.8%，1/120 例，OR=17.00，95%CI=1.83-158.04，p=0.007），12.5%（4/32 例 vs. 0%，0/120 例，OR=1.14，95%CI=1.00-1.30，p=0.002）和 12.5%（4/32 例 vs. 2.5%，3/120 例，OR=5.571，95%CI=1.79-2.32，p=0.036）。此外，C4A 和 C4B 缺乏症均与导致药物停用的药物不良反应相关（34.4%，11/32 例 C4A 缺乏症患者 vs. 14.2%，17/120 例对照组，OR=3.174，95%CI=1.30-7.74，p=0.009 和 28.7%，25/87 例 C4B 缺乏症患者，OR=2.44，95%CI=1.22-4.88，p=0.010）。
本研究报告的 C4A 或 C4B 纯合子缺乏症队列表明，C4 缺乏症可能与各种未记录的疾病相关。在研究这些选定的疾病关联时，C4 基因应被视为候选基因。
