An appraisal of the frequency and severity of noninfectious manifestations in primary immunodeficiencies: A study of a national retrospective cohort of 1375 patients over 10 years

Alligon, Mickaël; Mahlaoui, Nizar; Courteille, Virginie; Costes, Laurence; Afonso, Veronica; Randrianomenjanahary, Philippe; Vergnes, Nathalie de; Ranohavimparany, Anja; Vo, Duy An; Hafsa, I. Ben; Bach, Perrine; Benoît, Vincent; Garcelon, Nicolas; Fischer, Alain

doi:10.1016/j.jaci.2021.12.790

Cited by 12 publications

(8 citation statements)

References 35 publications

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“…We identified all patients diagnosed with CTLA4d in the French Reference Centre for Primary Immunodeficiencies (CEREDIH) registry from 2005 to February 2021. 10 Genetic screening was without charge for patients with suspicious symptoms. In addition, we surveyed neurology and internal medicine national society networks.…”

Section: Methodsmentioning

confidence: 99%

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Clinical, Radiologic, and Immunologic Features of Patients With CTLA4 Deficiency With Neurologic Involvement

Coustal¹,

Goulabchand²,

Labauge³

et al. 2023

Neurology

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Background and Objectives:CTLA4 deficiency (CTLA4d) is a disease with multisystem auto-immune features, including neurological manifestations. We aimed to describe neurological involvement in these patients.Methods:We performed a cross-sectional observational study using the French Reference Centre for Primary Immunodeficiencies (CEREDIH) registry, plus a surveillance in national society networks. Participants with confirmed CTLA4d and neurological involvement were included. Clinical, laboratory and radiological features were collected, as well as treatments. Available MRI were double-reviewed.Results:Among 70 patients with CTLA4d, 13 patients (21%) had neurological involvement. Neurological symptoms began at a median age of 18 [15-45] years, mostly occurring after systemic manifestations (median delay: 8.5 [4.5-10.5] years). Main symptoms included headaches, focal deficit (54% each) and seizures (38%). MRI detected at least one large contrast-enhancing lesion in eight patients. Lesions reminiscent of multiple sclerosis lesions were found in six patients. Cerebellar (6 patients) and large spinal cord lesions (3 patients) were common. Ten patients were treated with Abatacept, of whom nine (90%) showed good clinical and radiological response.Discussion:Neurologic involvement is common among patients with CTLA4d. Despite its rarity, and considering the suspected efficacy of Abatacept, neurologists should be aware of the characteristics of CTLA4d neurological involvement.

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Section: Methodsmentioning

confidence: 99%

“…CNS imaging was available for 9 of these patients. With a median follow-up of 4 [3][4][5][6][7][8][9][10][11][12] months, only 1 patient experienced a clinicoradiologic relapse (severe myelitis 4 months after treatment onset). None of the others had new lesion or gadolinium enhancement.…”

Section: Treatment Strategies and Outcomementioning

confidence: 99%

Clinical, Radiologic, and Immunologic Features of Patients With CTLA4 Deficiency With Neurologic Involvement

Coustal¹,

Goulabchand²,

Labauge³

et al. 2023

Neurology

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“…Noninfectious complications including autoimmunity, atopy, inflammation and malignancy have historically been linked to specific IEI; however, most data published thus far is either disease-specific or limited by cohort size [1,5–7]. A 2022 publication by Alligon et al [2 ▪▪ ] aims to address that, reporting on 10 years worth of longitudinal data on 1375 patients with IEI from the French National Reference Center for Primary Immune Deficiencies (CEREDIH) registry.…”

Section: Clinical Manifestations Of Autoimmunity and Autoinflammation...mentioning

confidence: 99%

“…What is more, these complications can arise across all age groups and all stages of disease, ranging from presenting complaints to late complications [1]. Historically, such complications were reported in specific IEI, but mounting evidence over the past years was further consolidated by the large retrospective study demonstrating that autoimmune, autoinflammatory and lymphoproliferative manifestations could be found across the entire IEI spectrum and could, in fact, be the only symptoms [2 ▪▪ ].…”

Section: Introductionmentioning

confidence: 99%

Autoimmune and autoinflammatory manifestations in inborn errors of immunity

Kačar

Markelj

Avčin

2022

Current Opinion in Allergy &Amp; Clinical Immunology

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Purpose of reviewAutoimmune and inflammatory complications have been shown to arise in all age groups and across the spectrum of inborn errors of immunity (IEI). This review aims to highlight recent ground-breaking research and its impact on our understanding of IEI.Recent findingsThree registry-based studies of unprecedented size revealed the high prevalence of autoimmune, inflammatory and malignant complications in IEI. Two novel IEI were discovered: an autoinflammatory relopathy, cleavage-resistant RIPK1-induced autoinflammatory syndrome, as well as an inheritable phenocopy of PD-1 blockade-associated complication (as seen in cancer therapy) manifesting with multiorgan autoimmunity and Mycobacterium tuberculosis infection. A study examining patients with partial RAG deficiency pinpointed the specific defects leading to the failure of central and peripheral tolerance resulting in wide-ranging autoimmunity. A novel variant of Immunodeficiency Polyendocrinopathy Enteropathy X-linked syndrome was described, associated with preferential expression of a FOXP3 isoform lacking exon 2, linking exon-specific functions and the phenotypes corresponding to their absence. Lastly, we touch on recent findings pertaining actinopathies, the prototypical IEI with autoimmune, inflammatory and atopic complications.SummaryDysregulated immunity has been associated with IEI since their discovery. Recently, large concerted efforts have shown how common these complications actually are while providing insight into normal and dysregulated molecular mechanisms, as well as describing novel diseases.

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“…They can be challenging to diagnose given the expanding and variable clinical phenotypes ( 2 , 3 ). Specifically, there is an increasing recognition that immune dysregulation can be an initial or predominant manifestation of a substantive portion of IEIs ( 4 , 5 ). Immune dysregulation can also have a large impact on disease treatment, monitoring, and outcomes.…”

mentioning

confidence: 99%

Editorial: Immune dysregulation in inborn errors of immunity

Wu,

Shahlaee,

Kwan

2023

Front. Pediatr.

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An appraisal of the frequency and severity of noninfectious manifestations in primary immunodeficiencies: A study of a national retrospective cohort of 1375 patients over 10 years

Cited by 12 publications

References 35 publications

Clinical, Radiologic, and Immunologic Features of Patients With CTLA4 Deficiency With Neurologic Involvement

Clinical, Radiologic, and Immunologic Features of Patients With CTLA4 Deficiency With Neurologic Involvement

Autoimmune and autoinflammatory manifestations in inborn errors of immunity

Editorial: Immune dysregulation in inborn errors of immunity

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