Monogenic Adult-Onset Inborn Errors of Immunity

Staels, Frederik; Collignon, Tom; Betrains, Albrecht; Gerbaux, Margaux; Willemsen, Mathijs; Humblet-Baron, Stéphanie; Liston, Adrian; Vanderschueren, Steven; Schrijvers, R.

doi:10.3389/fimmu.2021.753978

Cited by 23 publications

(22 citation statements)

References 187 publications

(294 reference statements)

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“…11,13 In European registries, B-cell disorders are the most common type of immunodeficiency, accounting for approximately 50%-60% of all IEI with most presenting in adulthood, in part due to a less severe phenotype. 10,12,13,33 Reflecting this, the majority (53%) were classified with a predominant antibody deficiency (IUIS III) where presentation with neutropenia showed significant association (Figures 2, 4). Interestingly, IUIS I and II are more common in populations with higher consanguinity.…”

Section: Cohort Characteristicsmentioning

confidence: 84%

Peripheral‐blood cytopenia, an early indicator of inborn errors of immunity

et al. 2022

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Summary Inborn errors of immunity (IEI) are inherited monogenic disorders resulting in defective immune response. Non‐infectious presentations are increasingly more apparent. Widely available, cost‐effective early indicators are needed. Peripheral‐blood cytopenia may be a presenting laboratory feature or an observed secondary phenomenon. This retrospective review of the South African Primary Immunodeficiency Registry (SAPIDR) aimed to assess the haematological indices at presentation and their association with the International Union of Immunological Societies (IUIS) 2019 IEI classification and mortality. Of 396 patients on the SAPIDR, 66% (n = 257) had available haematological results. Sixty percent were males and 85% under 18 years. A majority (53%) had predominantly antibody deficiency. At presentation, infection was prominent (86%) followed by cytopenia (62%). Neutropenia was associated with IUIS III [odds ratio (OR) 3.65, confidence interval (CI) 1.44–9.25], thrombocytopenia with IUIS II (OR 14.39, CI 2.89–71.57), lymphopenia with IUIS I (OR 12.16, CI 2.75–53.73) and pancytopenia with IUSI I (OR 12.24, CI 3.82–39.05) and IUIS II (OR 5.99, CI 2.80–12.76). Cytopenia showed shorter overall survival (OR 2.81, CI 1.288–4.16). Cytopenias that are severe, persistent, unusual and/or recurrent should prompt further investigation for IEI. The full blood count and leucocyte differential may facilitate earlier identification and serve as an adjunct to definitive molecular classification.

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Section: Cohort Characteristicsmentioning

confidence: 84%

Peripheral‐blood cytopenia, an early indicator of inborn errors of immunity

et al. 2022

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“…Thanks to the introduction of next generation sequencing (NGS) methods in the last ten years, more than 400 gene defects implied in IEIs have been identified [29]. Regarding CVID, only 20% of cases are caused by monogenic defects; the remaining 80% derives from polygenic variants and/or from epigenetic alterations [30,31]. Interestingly, a study recently published by Khandia et al considering a panel of 42 genes involved both in PID and cancer highlighted how these genes are under a selection pressure [32].…”

Section: Discussionmentioning

confidence: 99%

Common Variable Immunodeficiency in Elderly Patients: A Long-Term Clinical Experience

et al. 2022

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Background: Common variable immunodeficiency (CVID) is a complex, predominantly antibody deficiency usually diagnosed between 20–40 years. Few data about elderly patients are reported in the literature. Our aim was to evaluate the clinical phenotypes of elderly patients with CVID. Method: A retrospective analysis of adult patients with CVID was performed in our Referral Centre, focusing on the main differences between “older” patients (≥ 65 years at the diagnosis) and “younger” patients (< 65 years). Results: The data from 65 younger and 13 older patients followed up for a median period of 8.5 years were available. At diagnosis, recurrent infections represented the only clinical manifestation in 61% and 69% of younger and older patients, respectively. The incidence of autoimmune diseases was higher in elderly patients compared with younger ones (30 vs. 18%, respectively). During the follow-up, the incidence of autoimmune disorders and enteropathy increased in the younger patients whereas neoplasia became the most prevalent complication in the elderly (38%). All patients received a replacement therapy with immunoglobulin, with good compliance. Conclusion: CVID occurrence in elderly patients is rarely described; therefore, the clinical characteristics are not completely known. In our series, neoplasia became the most prevalent complication in the elderly during the follow-up. In elderly patients, 20% SCIg was as safe as in the younger ones, with good compliance. A genetic analysis is important to confirm the diagnosis, identify specific presentations in the different ages, clarify the prognosis and guide the treatment. Future clinical research in this field may potentially help to guide their care.

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“…При этом у многих пациентов, которым диагноз САВЗ впервые был поставлен во взрослом возрасте, в анамнезе имели место эпизоды необъяснимой рецидивирующей лихорадки и другие клинические и лабораторные проявления воспаления. Полагают, что особенности генетической предрасположенности (соматический мозаицизм, носительство генных мутаций с низкой пенетрантностью, гетерозиготность или сложная гомозиготность), характер сопутствующих нарушений врожденного иммунитета, коморбидная патология, факторы внешней среды являются потенциальными причинами «накопления» САВЗ у лиц взрослого возраста [13][14][15][257][258][259]. Несмотря на постоянное совершенствование методов молекулярной диагностики моногенных САВЗ, следует принимать во внимание высокую стоимость генетического тестирования (метода секвенирования ДНК Сэнгера), клинические и экономические обоснования для проведения которого не сформулированы.…”

Section: Discussionunclassified

“…Круг ИВЗ, при которых обсуждается патогенетическое значение ИЛ-1, неуклонно расширяется [7,11,12]. К ним в первую очередь относятся гетерогенная группа системных моногенных и полигенных (мультифакториальных) аутовоспалительных заболеваний (САВЗ) у детей и взрослых [13][14][15][16][17][18]. Подавление «провоспалительных» эффектов ИЛ-1 с использованием генно-инженерных биологических препаратов (ГИБП) рассматривается как перспективный подход к лечению этих заболеваний [18][19][20][21][22].…”

Section: моногенные аутоиммунные заболеванияunclassified

The role of interleukin 1 in the development of human diseases: focus on Anakinra (IL-1 receptor antagonist)

Насонов

Samsonov

2022

Naučno-praktičeskaâ revmatologiâ

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According to modern concepts, human immune-mediated inflammatory diseases (IMIDs), depending on the prevailing mechanisms of immunopathogenesis, are divided into two main categories – autoimmune and autoinflammatory.At the same time, both autoimmune and autoinflammatory mechanisms are involved in the pathogenesis of most IMIDs, the complex interaction of which is reflected in the polymorphism of clinical manifestations, course variants, outcomes, and therapy efficacy. It is assumed that hyperproduction of cytokines of the interleukin (IL) 1 family, which is one of the key regulators of innate immunity, determines the “crossover” between the mechanisms of autoinflammation and autoimmunity in IMIDs. Anakinra is currently used in clinical practice to suppress the pathological effects of IL-1. An analysis of the results of the clinical use of Anakinra indicates that treatment with this drug should be considered as a promising direction in the pharmacotherapy of systemic autoinflammatory diseases (SAIDs) and critical conditions in children and adults associated with the development of hyperinflammation. The main directions of the Anakinra clinical research program are presented, including: determining the place of the drug in the implementation of the "Treat to Target" strategy and personalization of therapy, primarily in patients with “resistant” (difficult-to-treat) subtype of rheumatoid arthritis and comorbid pathology, as well as with severe forms of microcrystalline arthritis; the possibility of using Anakinra to improve the early diagnosis of SAIDs in children and adults; creation of the Russian register of patients with SAIDs, who are potentially indicated for treatment with Anakinra.

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Monogenic Adult-Onset Inborn Errors of Immunity

Cited by 23 publications

References 187 publications

Peripheral‐blood cytopenia, an early indicator of inborn errors of immunity

Peripheral‐blood cytopenia, an early indicator of inborn errors of immunity

Common Variable Immunodeficiency in Elderly Patients: A Long-Term Clinical Experience

The role of interleukin 1 in the development of human diseases: focus on Anakinra (IL-1 receptor antagonist)

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