title: Infections Revealing Complement Deficiency in Adults: A French Nationwide Study Enrolling 41 Patients.
abstract: Complement system is a part of innate immunity, its main function is to protect human from bacterial infection. As genetic disorders, complement deficiencies are often diagnosed in pediatric population. However, complement deficiencies can also be revealed in adults but have been poorly investigated. Herein, we describe a case series of infections revealing complement deficiency in adults to study clinical spectrum and management of complement deficiencies.A nationwide retrospective study was conducted in French university and general hospitals in departments of internal medicine, infectious diseases enrolling patients older than 15 years old who had presented at least one infection leading to a complement deficiency diagnosis.Forty-one patients included between 2002 and 2015 in 19 different departments were enrolled in this study. The male-to-female ratio was 1.3 and the mean age at diagnosis was 28 ± 14 (15-67) years. The main clinical feature was Neisseria meningitidis meningitis 75% (n = 31/41) often involving rare serotype: Y (n = 9) and W 135 (n = 7). The main complement deficiency observed was the common final pathway deficiency 83% (n = 34/41). Half of the cohort displayed severe sepsis or septic shock at diagnosis (n = 22/41) but no patient died. No patient had family history of complement deficiency. The mean follow-up was 1.15 ± 1.95 (0.1-10) years. Half of the patients had already suffered from at least one infection before diagnosis of complement deficiency: meningitis (n = 13), pneumonia (n = 4), fulminans purpura (n = 1), or recurrent otitis (n = 1). Near one-third (n = 10/39) had received prophylactic antibiotics (cotrimoxazole or penicillin) after diagnosis of complement deficiency. The vaccination coverage rate, at the end of the follow-up, for N meningitidis, Streptococcus pneumonia, and Haemophilius influenzae were, respectively, 90% (n = 33/37), 47% (n = 17/36), and 35% (n = 14/34).This large study emphasizes that complement deficiencies can be revealed in adults by infectious episodes. Most of them were meningococcal infections revealing common final pathway deficiency. To avoid undiagnosis or late diagnosis, adult displaying first episode of N meningitidis infection should be tested for complement deficiency.
authors.affiliation: From the CHU de Caen, Department of Internal Medicine, Caen (AA-V, BB), Department of Infectious Diseases, Nouvelle Calédonie University Hospital, Nouvelle Calédonie (ED, MJ), Laboratory of Immunology, Grenoble University Hospital, Grenoble (DP, AD), Department of Internal Medicine, Grenoble University Hospital, Grenoble, Department of Internal Medicine, Beaujon Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris (BF), Department of Clinical Immunology, Saint-Louis University Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris (CF, DB), Department of Internal Medicine, Robert Ballanger General Hospital, Aulnay sous Bois (MAB), Department of Internal Medicine, Hôpital d'Instruction des Armées, Metz (LK), Department of Internal Medicine, Toulouse University Hospital, UMR 1027 INSERM University of Toulouse; CIC 1436, Toulouse (GM), Department of Internal Medicine, Brest University Hospital, Brest (HA), Department of Paediatric Intensive Care Unit, Lyon University Hospital, Lyon (FV), Department of Infectious Diseases, Nîmes University Hospital, Nîmes (CL), Department of Infectious Diseases, Raymond Poincaré University Hospital, Garches (BD), Department of Medicine, Colmar General Hospital, Colmar (MM), Department of Infectious Diseases, Nantes University Hospital, Nantes (CB, NA), Department of Infectious Diseases, Saint Etienne University Hospital, Saint Etienne (FL), Department of Internal Medicine, Créteil Hospital, Créteil (AF), Department of Infectious Diseases, Tours University Hospital, Tour (RB), Department of Internal Medicine, Rennes University Hospital, Rennes (AP), Laboratory of Immunology, Team Dentritic Cells Physiology, Cochin Institute (SI); and Laboratory of Immunology, Européen Georges Pompidou University Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris (VF-B), France.
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mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D001424:Bacterial Infections / Q000188:drug therapy / Q000276:immunology*; D015938:Complement Membrane Attack Complex / Q000172:deficiency; D003165:Complement System Proteins / Q000172:deficiency*; D057210:Delayed Diagnosis; D005260:Female; D005602:France; D006801:Humans; D008297:Male; D008585:Meningitis, Meningococcal / Q000276:immunology / Q000382:microbiology; D008875:Middle Aged; D009345:Neisseria meningitidis; D010033:Otitis Media / Q000276:immunology; D011014:Pneumonia / Q000276:immunology; D055665:Purpura Fulminans / Q000276:immunology; D012189:Retrospective Studies; D018805:Sepsis / Q000276:immunology; D012772:Shock, Septic / Q000276:immunology; D055815:Young Adult
chemical_list: D015938:Complement Membrane Attack Complex; D003165:Complement System Proteins