Autoimmune and inflammatory manifestations occur frequently in patients with primary immunodeficiencies

Fischer, Alain; Provot, Johan; Alcaïs, Alexandre; Mahlaoui, Nizar; Adoue, D.; Aladjidi, Nathalie; Amoura, Zahir; Arlet, P.; Armari‐Alla, Corinne; Bader‐Meunier, Brigitte; Barlogis, Vincent; Bayart, Sophie; Beaurain, Beatrice; Bertrand, Yves; Bienvenu, Boris; Blanche, Stéphane; Bodet, Damien; Bonnotte, B.; Borie, R.; Boutard, Patrick; Briandet, Claire; Brion, Jean‐Paul; Brito, Carolina; Brouard, J.; Catherinot, Émilie; Chandesris, Olivia; Cohen-Beaussant, Sarah; Coignard-Biehler, Hélène; Costes, Laurence; Couderc, Louis‐Jean; Couillault, G.; Courteille, Virginie; Curlier, Elodie; Basile, Geneviève de Saint; Deméocq, F.; Vergnes, Nathalie de; Devoldère, Catherine; Deville, Anne; Donadieu, Jean; Doré, Éric; Dulieu, Fabienne; Durieu, I.; Edan, Christine; Werle, Natacha Entz; Fieschi, Claire; Fouyssac, Fanny; Frange, Pierre; Gajdos, Vincent; Galicier, Lionel; Gandemer, Virginie; Gardembas, Martine; Gaud, C.; Grosbois, B.; Guillerm, Gaëlle; Hachulla, É.; Hamidou, M.; Héritier, Sébastien; Hermine, Olivier; Hoarau, C.; Hoën, Bruno; Hot, A.; Humbert, S.; Jaccard, Arnaud; Jacquot, Serge; Jaı̈s, Jean-Philippe; Jaussaud, R.; Jeandel, Pierre-Yves; Jeziorski, Éric; Kébaïli, Kamila; Korganow, Anne-Sophie; Labrune, Philippe; Lambotte, Olivier; Lanternier, Fanny; Larroche, Claire; Quellec, A. Le; Moigne, E. Le; Moing, Vincent Le; Lebranchu, Yvon; Lecuit, Marc; Lefèvre, Guillaume; Lemal, Richard; Moine, Philippe; Te, Valérie Li Thiao; Lortholary, Olivier; Lutz, Patrick; Magérus-Chatinet, Aude; Malphettes, Marion; Marie‐Cardine, Aude; Silva, Nicolas Martin; Masseau, A.; Massot, Christian; Mazingue, Françoise; Merlin, E.; Gautier, Michel; Millot, Frédéric; Minckes, Odile; Monlibert, Béatrice; Monpoux, Fabrice; Moshous, Despina; Mouthon, Luc; Munzer, Martine; Neven, Bénédicte; Nové-Josserand, R.; Oksenhendler, Éric; Marie, O; Pagnier, Anne; Pasquali, Jean‐Louis; Pasquet, Marlène; Pellier, Isabelle; Pérel, Yves; Perlat, Antoinette; Pïcard, Capucine; Piguet, Christophe; Plantaz, Dominique; Quartier, Pierre; Rieux‐Laucat, Frédéric; Roblot, P.; Roger, Pierre‐Marie; Rohrlich, Pierre‐Simon; Royer, Bruno; Salle, V.; Sarrot-Reynauld, F.; Servettaz, Amélie; Stéphan, Jean-Louis; Schleinitz, N.; Suarez, Félipe; Swiader, L.; Taque, Sophie; Thomas, Caroline; Tournilhac, Olivier; Thumerelle, C.; Vannier, Jean‐Pierre; Viallard, Jean‐François

doi:10.1016/j.jaci.2016.12.978

Cited by 247 publications

(222 citation statements)

References 30 publications

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“…Nearly a quarter of patients presented with symptoms other than recurrent infections. Non‐infectious presentations such as autoimmune cytopaenias, inflammatory bowel disease and malignancy are being recognized increasingly as possible presentations of PID . The median diagnostic delay for patients who presented with malignancy is 4 years, the highest amongst the presenting symptoms recorded by our registry.…”

Section: Discussionmentioning

confidence: 95%

The United Kingdom Primary Immune Deficiency (UKPID) registry 2012 to 2017

Shillitoe

Bangs

Guzmán

et al. 2018

Clinical and Experimental Immunology

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This is the second report of the United Kingdom Primary Immunodeficiency (UKPID) registry. The registry will be a decade old in 2018 and, as of August 2017, had recruited 4758 patients encompassing 97% of immunology centres within the United Kingdom. This represents a doubling of recruitment into the registry since we reported on 2229 patients included in our first report of 2013. Minimum PID prevalence in the United Kingdom is currently 5·90/100 000 and an average incidence of PID between 1980 and 2000 of 7·6 cases per 100 000 UK live births. Data are presented on the frequency of diseases recorded, disease prevalence, diagnostic delay and treatment modality, including haematopoietic stem cell transplantation (HSCT) and gene therapy. The registry provides valuable information to clinicians, researchers, service commissioners and industry alike on PID within the United Kingdom, which may not otherwise be available without the existence of a well-established registry.

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Section: Discussionmentioning

confidence: 95%

The United Kingdom Primary Immune Deficiency (UKPID) registry 2012 to 2017

Shillitoe

Bangs

Guzmán

et al. 2018

Clinical and Experimental Immunology

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“…This prevalence of autoimmune cytopenia is strikingly higher than among the general population, in whom ITP has been estimated to affect between 8 and 12 in 100,000 [14]; AIHA between 1 and 17 per 100,000 [15, 16]; and autoimmune neutropenia 1 in 100,000, among in children aged 1 to 10 years [17]. Compared to the USIDNET Registry, other CVID patient registries report higher prevalence of autoimmune cytopenias: a French report of 408 CVID patients and a US cohort of 473 CVID patients noted one or more autoimmune cytopenia in 14 to 18% of patients [4, 8, 18]. While 13.2 and 14.2% of CVID patients had a diagnosis of ITP in the French and New York cohorts respectively, only 7.4% were noted as having had ITP in USIDNET.…”

Section: Discussionmentioning

confidence: 99%

“…The increased prevalence of these complications in the +AC CVID patients suggests that these conditions originate from the immune dysregulation and dysfunction contributing to their specific CVID phenotype. Further, the conditions that were increased in the +AC group have been associated with increased morbidity and mortality [3, 4, 18]. As the first episode of autoimmune cytopenia most often develops early in the course of CVID [8–10, 19, 20], autoimmune cytopenia may predict a more complicated course, necessitating closer monitoring for various non-infectious complications.…”

Section: Discussionmentioning

confidence: 99%

Autoimmune Cytopenias and Associated Conditions in CVID: a Report From the USIDNET Registry

et al. 2017

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Purpose Autoimmune cytopenia is frequently a presenting manifestation of common variable immune deficiency (CVID). Studies characterizing the CVID phenotype associated with autoimmune cytopenias have mostly been limited to large referral centers. Here, we report prevalence of autoimmune cytopenias in CVID from the USIDNET Registry and compare the demographics and clinical features of patients with and without this complication. Methods Investigators obtained demographic, laboratory, and clinical data on CVID patients within the USIDNET Registry. Patients were considered to have autoimmune cytopenia if they had a diagnosis of hemolytic anemia, immune thrombocytopenia (ITP), or autoimmune neutropenia. Baseline characteristics and associated complications of those with autoimmune cytopenia (+AC) and those without (−AC) were compared. Results Of 990 CVID patients included in the analysis, 10.2% (N = 101) had a diagnosis consistent with autoimmune cytopenia: ITP was diagnosed in 7.4% (N = 73), hemolytic anemia in 4.5% (N = 45), and autoimmune neutropenia in 1% (N = 10). Age at diagnosis, gender, and baseline Ig values did not differ between the +AC and −AC groups. The +AC group was significantly more likely to have one or more other CVID-associated non-infectious complications (OR = 2.9; 95%-CI: 1.9–4.6, P < 0.001), including lymphoproliferation, granulomatous disease, lymphomas, hepatic disease, interstitial lung diseases, enteropathy, and organ-specific autoimmunity. Conclusions Autoimmune cytopenias are a common manifestation in CVID and are likely to be associated with other non-infectious CVID-related conditions. In light of prior studies showing increased morbidity and mortality in CVID patients with such complications, a diagnosis of autoimmune cytopenia may have prognostic significance in CVID.

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“…In this paradigm, immune deficiency ultimately predisposes to exaggerated inflammatory responses and indeed, is increasingly recognized today in the field of primary immunodeficiencies (PIDs) . A recent analysis of French National Primary Immunodeficiencies Registry (CEDEDIH) showed that one or more autoimmune/inflammatory symptoms are observed in 26.2% of patients with primary immunodeficiency . This paradox of immune deficiency leading to compensatory inflammation is only recently appreciated, as traditionally immune deficiency was only associated with infection susceptibility.…”

Section: Concluding: the Paradox Of Immune Deficiency And Inflammatiomentioning

confidence: 99%

Primary immunodeficiencies reveal the essential role of tissue neutrophils in periodontitis

Silva

Brenchley

Moutsopoulos

2018

Immunological Reviews

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Summary Periodontitis is a common human inflammatory disease. In this condition, microbiota trigger excessive inflammation in oral mucosal tissues surrounding the dentition, resulting in destruction of tooth‐supporting structures (connective tissue and bone). While susceptibility factors for common forms of periodontitis are not clearly understood, studies in patients with single genetic defects reveal a critical role for tissue neutrophils in disease susceptibility. Indeed, various genetic defects in the development, egress from the bone marrow, chemotaxis, and extravasation are clearly linked to aggressive/severe periodontitis at an early age. Here, we provide an overview of genetic defects in neutrophil biology that are linked to periodontitis. In particular, we focus on the mechanisms underlying Leukocyte Adhesion Deficiency‐I, the prototypic Mendelian defect of impaired neutrophil extravasation and severe periodontitis.

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Autoimmune and inflammatory manifestations occur frequently in patients with primary immunodeficiencies

Abstract: Our results provide the basis for a detailed prospective evaluation of autoimmunity and inflammation in the context of PIDs, with a view to accurately assessing these risks and describing the possible effect of medical intervention.

Cited by 247 publications

References 30 publications

The United Kingdom Primary Immune Deficiency (UKPID) registry 2012 to 2017

The United Kingdom Primary Immune Deficiency (UKPID) registry 2012 to 2017

Autoimmune Cytopenias and Associated Conditions in CVID: a Report From the USIDNET Registry

Primary immunodeficiencies reveal the essential role of tissue neutrophils in periodontitis

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