Inherited PD-1 deficiency underlies tuberculosis and autoimmunity in a child

Ogishi, Masato; Yang, Rui; Aytekin, Caner; Langlais, David; Bourgey, Mathieu; Khan, Taushif; Ali, Fatima; Rahman, Mahbuba; Delmonte, Ottavia M.; Chrabieh, Maya; Zhang, Peng; Gruber, Conor; Pelham, Simon J.; Spaan, András N.; Rosain, Jérémie; Lei, Wei‐Te; Drutman, Scott; Hellmann, Matthew D.; Callahan, Margaret K.; Adamow, Matthew; Wong, Phillip; Wolchok, Jedd D.; Rao, Geetha; Cindy, S.; Nakajima, Yuka; Yaguchi, Tomonori; Chamoto, Kenji; Williams, S.; Émile, Jean-François; Rozenberg, Flore; Glickman, Michael S.; Rapaport, Franck; Kerner, Gaspard; Allington, Garrett; Tezcan, İlhan; Çağdaş, Deniz; Hoşnut, Ferda Özbay; Doğu, Figen; İkincioğulları, Aydan; Rao, V. Koneti; Kainulainen, Leena; Béziat, Vivien; Bustamante, Jacinta; Vilarinho, Sílvia; Lifton, Richard P.; Boisson, Bertrand; Abel, Laurent; Bogunovic, Dusan; Marr, Nico; Notarangelo, Luigi D.; Tangye, Stuart G.; Honjo, Tasuku; Gros, Philippe; Boisson–Dupuis, Stéphanie; Casanova, Jean‐Laurent

doi:10.1038/s41591-021-01388-5

Cited by 72 publications

(53 citation statements)

References 71 publications

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“…13 With respect to PD-1/PD-L1, PD-1-deficient mice are highly susceptible to TB infection, 14 15 and a case of inherited PD-1 deficiency associating with TB has very recently been reported. 16 Given the emerging evidence of increased infection in patients treated with ICIs and evidence that immune checkpoint deficiency can be associated with recurrent infections, we were interested in evaluating the infectious sequelae of ICI therapy. Furthermore, we aimed to characterise the pattern of these infectious complications to inform future clinical management strategies and the associated research agenda.…”

Section: Consequences Of Natural Immune Checkpoint Loss Of Functionmentioning

confidence: 99%

Infections due to dysregulated immunity: an emerging complication of cancer immunotherapy

Morelli

Fujita

Redelman-Sidi

et al. 2021

Thorax

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Immune checkpoint inhibitors (ICIs) have revolutionised cancer treatment. However, immune-related adverse events (irAEs) are a common side effect which can mimic infection. Additionally, treatment of irAEs with corticosteroids and other immunosuppressant agents can lead to opportunistic infection, which we have classed as immunotherapy infections due to immunosuppression. However, emerging reports demonstrate that some infections can be precipitated by ICIs in the absence of immunosuppressive treatment, in contrast to the majority of reported cases. These infections are characterised by a dysregulated inflammatory immune response, and so we propose they are described as immunotherapy infections due to dysregulated immunity. This review summarises the rapidly emerging evidence of these phenomena and proposes a new framework for considering infection in the context of cancer immunotherapy.

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Section: Consequences Of Natural Immune Checkpoint Loss Of Functionmentioning

confidence: 99%

Infections due to dysregulated immunity: an emerging complication of cancer immunotherapy

Morelli

Fujita

Redelman-Sidi

et al. 2021

Thorax

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“…Recently, a rare, homozygous frameshift mutation (c.105dupC, p.T36Hfs*70) in PDCD1 was identified in a patient with tuberculosis and autoimmunity (96). The mutation was shown to abrogate PD-1 expression.…”

Section: Pdcd1 Deficiencymentioning

confidence: 99%

Inborn Errors of Immunity and Their Phenocopies: CTLA4 and PD-1

Hao

Cook

2022

Front. Immunol.

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Elucidating links between genotype and phenotype in patients with rare inborn errors of immunity (IEIs) provides insights into mechanisms of immune regulation. In many autosomal dominant IEIs, however, variation in expressivity and penetrance result in complex genotype-phenotype relations, while some autosomal recessive IEIs are so rare that it is difficult to draw firm conclusions. Phenocopies arise when an environmental or non-genetic factor replicates a phenotype conferred by a specific genotype. Phenocopies can result from therapeutic antibodies or autoantibodies that target a protein to replicate aspects of the phenotype conferred by mutations in the gene encoding the same protein. Here, we consider IEIs arising from rare genetic variants in CTLA4 and PDCD1 and compare clinical and laboratory manifestations arising as drug-induced phenocopies (immune related adverse events, IRAEs) in cancer patients treated with immune checkpoint inhibitors (ICI) and identify outstanding questions regarding mechanism of disease.

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“…Endocrinopathy would be comorbidity of recently identified IEI. Inherited PD-1 deficiency and activated PI3Kd syndrome (APDS) type 2, would associate with T1DM (38)(39)(40). Familial thyroiditis and T1DM are reported in patients with A20 (TNFAIP3) haploinsufficiency (41,42).…”

Section: Pathophysiology Of Endocrinopathy In Iei Autoimmunementioning

confidence: 99%

Endocrinopathies in Inborn Errors of Immunity

et al. 2021

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Inborn errors of immunity (IEI), caused by hereditary or genetic defects, are a group of more than 400 disorders, in which the immune system, including lymphocytes, neutrophils, macrophages, and complements, does not function properly. The endocrine system is frequently affected by IEI as an associated clinical feature and a complex network of glands which regulate many important body functions, including growth, reproduction, homeostasis, and energy regulation. Most endocrine disorders associated with IEI are hypofunction which would be treated with supplementation therapy, and early diagnosis and appropriate management are essential for favorable long-term outcomes in patients with IEI. In this review, we aimed to comprehensively summarize and discuss the current understanding on the clinical features and the pathophysiology of endocrine disorders in IEI. This review is composed with three parts. First, we discuss the two major pathophysiology of endocrinopathy in IEI, autoimmune response and direct effects of the responsible genes. Next, the details of each endocrinopathy, such as growth failure, hypothyroidism, hypoparathyroidism, adrenal insufficiency, diabetes mellitus (DM) are specified. We also illustrated potential endocrinopathy due to hematopoietic stem cell transplantation, including hypogonadism and adrenal insufficiency due to glucocorticoid therapy.

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Inherited PD-1 deficiency underlies tuberculosis and autoimmunity in a child

Cited by 72 publications

References 71 publications

Infections due to dysregulated immunity: an emerging complication of cancer immunotherapy

Infections due to dysregulated immunity: an emerging complication of cancer immunotherapy

Inborn Errors of Immunity and Their Phenocopies: CTLA4 and PD-1

Endocrinopathies in Inborn Errors of Immunity

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