Spectrum of Systemic Auto-Inflammatory Diseases in India: A Multi-Centric Experience

Suri, Deepti; Jindal, Ankur Kumar; Vignesh, Pandiarajan; Gupta, Anju; Pilania, Rakesh Kumar; Joshi, Vibhu; Arora, Kanika; Kumrah, Rajni; Anjani, Gummadi; Aggarwal, Amita; Phadke, Shubha R.; Aboobacker, Fouzia N.; George, Biju; Edison, Eunice Sindhuvi; Desai, Mukesh; Taur, Prasad; Gowri, Vijaya; Pandrowala, Ambreen; Bhattad, Sagar; Kanakia, Swati; Gottorno, Marco; Ceccherini, Isabella; Jesús, Adriana Almeida de; Goldbach‐Mansky, Raphaela; Hershfield, Michael S.; Singh, Surjit

doi:10.3389/fimmu.2021.630691

Cited by 13 publications

(12 citation statements)

References 45 publications

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“…Of the thirty-one sequence variants in the PLCG2 gene listed in Infevers [ 7 ], two pathogenic, one variant of unknown significance (VUS), one likely benign, and five so far not classified PLCG2 gene variants displayed an APLAID phenotype and three not classified PLCG2 gene variants presented a PLAID phenotype [ 3 , 5 , 8 , 9 , 10 , 11 , 12 , 13 ]. In addition, five other papers were identified in the PubMed search, which fulfilled the inclusion criteria [ 14 , 15 , 16 , 17 , 18 ]. Data fulfilling inclusion criteria were analyzed for genetic, clinical and immunology characteristics ( Table 2 and Table 3 ).…”

Section: Resultsmentioning

confidence: 99%

“…Several patients diagnosed as PLAID had evidence for cold-induced urticaria, increased susceptibility for recurrent infections, signs of autoimmunity and allergic diseases and immunologic findings (reduced immunoglobulins, low numbers of circulating class switched memory B-cells, reduced NK cells) [ 3 , 10 , 18 ]. Several patients diagnosed as APLAID had the following clinical and laboratory characteristics: cutaneous findings (rashes, erythema, granulomas, cutis laxa and vesiculo-pustular lesions), eye inflammation, recurrent infections, abdominal pain and inflammatory bowel disease, musculoskeletal complaints, immunologic findings (reduced/normal immunoglobulins, reduced circulating class-switched CD27+ memory B-lymphocytes and decreased/normal NK cells) [ 5 , 8 , 9 , 12 , 14 , 15 , 16 , 17 , 18 ]. Data were compared with patients’ characteristics from our case series, highlighting an overlap of characteristics previously reported for the PLAID and APLAID syndrome.…”

Section: Resultsmentioning

confidence: 99%

“…All five patients in this case series had clinical and laboratory similarities with previously described patients diagnosed as PLAID/APLAID. The patients in this case series showed PLAID characteristics, such as cold-induced urticaria [ 3 , 10 ] and APLAID characteristics, such as eye inflammation, musculoskeletal complaints and no circulating antibodies [ 5 , 8 , 9 , 12 , 14 , 15 , 16 ]. All patients had recurrent upper airway infections, abdominal pain, episodic diarrhea and normal T-cell function, as previously described in several PLAID and APLAID patients [ 3 , 5 , 8 , 9 , 12 , 14 , 15 , 16 ].…”

Section: Discussionmentioning

confidence: 99%

“…The patients in this case series showed PLAID characteristics, such as cold-induced urticaria [ 3 , 10 ] and APLAID characteristics, such as eye inflammation, musculoskeletal complaints and no circulating antibodies [ 5 , 8 , 9 , 12 , 14 , 15 , 16 ]. All patients had recurrent upper airway infections, abdominal pain, episodic diarrhea and normal T-cell function, as previously described in several PLAID and APLAID patients [ 3 , 5 , 8 , 9 , 12 , 14 , 15 , 16 ]. In addition, they had normal NK cells, similar to several APLAID patients [ 5 , 8 , 9 , 14 ].…”

Section: Discussionmentioning

confidence: 99%

“…This case series contains five patients with a rare disease (estimated prevalence <1/1,000,000; ). The majority of other published reports include one to three patients [ 5 , 8 , 9 , 10 , 12 , 14 , 15 , 16 , 17 , 18 ]. However, Ombrello et al presented data of 27 patients from three families [ 3 ].…”

Section: Discussionmentioning

confidence: 99%

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Variant in the PLCG2 Gene May Cause a Phenotypic Overlap of APLAID/PLAID: Case Series and Literature Review

Welzel

Oefelein²,

Holzer

et al. 2022

JCM

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Background: Variants in the phospholipase C gamma 2 (PLCG2) gene can cause PLCG2-associated antibody deficiency and immune dysregulation (PLAID)/autoinflammation and PLCG2-associated antibody deficiency and immune dysregulation (APLAID) syndrome. Linking the clinical phenotype with the genotype is relevant in making the final diagnosis. Methods: This is a single center case series of five related patients (4–44 years), with a history of autoinflammation and immune dysregulation. Clinical and laboratory characteristics were recorded and a literature review of APLAID/PLAID was performed. Results: All patients had recurrent fevers, conjunctivitis, lymphadenopathy, headaches, myalgia, abdominal pain, cold-induced urticaria and recurrent airway infections. Hearing loss was detected in two patients. Inflammatory parameters were slightly elevated during flares. Unswitched B-cells were decreased. Naïve IgD+CD27− B-cells and unswitched IgD+CD27+ B-cells were decreased; switched IgD-CD27+ B-cells were slightly increased. T-cell function was normal. Genetic testing revealed a heterozygous missense variant (c.77C>T, p.Thr26Met) in the PLCG2 gene in all patients. Genotype and phenotype characteristics were similar to previously published PLAID (cold-induced urticaria) and APLAID (eye inflammation, musculoskeletal complaints, no circulating antibodies) patients. Furthermore, they displayed characteristics for both PLAID and APLAID (recurrent infections, abdominal pain/diarrhea) with normal T-cell function. Conclusion: The heterozygous missense PLCG2 gene variant (c.77C>T, p.Thr26Met) might cause phenotypical overlap of PLAID and APLAID patterns.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Variant in the PLCG2 Gene May Cause a Phenotypic Overlap of APLAID/PLAID: Case Series and Literature Review

Welzel

Oefelein²,

Holzer

et al. 2022

JCM

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Profile of 208 patients with inborn errors of immunity at a tertiary care center in South India

Bhattad,

Mohite,

Singh

et al. 2023

Clin Exp Med

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Primary immune de ciencies better known as Inborn Errors of Immunity (IEI) are a heterogeneous group of disorders that predispose affected individuals to infections, allergy, autoimmunity, autoin ammation, and malignancies.. Inborn Errors of Immunity are increasingly being recognized in the Indian subcontinent. Two hundred and eight patients diagnosed with an IEI during February 2017 to November 2021 at a tertiary care centre in South India were included in the study. The clinical features, laboratory ndings including microbiologic and genetic data, treatment & outcome details were analyzed. The diagnosis of IEI was con rmed in a total of 208 patients (198 kindreds) based on relevant immunological tests and/or genetic tests. The male to female ratio was 1.8:1. The most common IEI in our cohort was SCID (17.7%) followed by CGD (12.9%) and CVID (9.1%). We also had a signi cant proportion of patients with DOCK8 de ciency (7.2%), LAD (6.2%), and six patients (2.8%) with autoin ammatory diseases. Autoimmunity was noted in forty-six (22%) patients during the course of their illness. Molecular testing was performed in 152 patients by exome sequencing on NGS platform and a genetic variant was reported in 132 cases. Twenty-nine children underwent 34 HSCT, and 135 patients remain on supportive therapy such as immunoglobulin replacement and/or antimicrobial prophylaxis. Fifty-nine (28.3%) patients died during the study period and infections were the predominant cause of mortality. Seven families underwent prenatal testing in the subsequent pregnancy. We describe the pro le of 208 patients with IEI and to the best of our knowledge, this represents the largest data on IEI from the Indian subcontinent reported so far.Patient details such as the age at onset of symptoms, clinical presentation, age at diagnosis, family history, laboratory ndings including microbiologic data, treatment & outcome details were recorded. Clinical details included both infectious and noninfectious manifestations (allergy, autoimmunity, malignancy, etc) at presentation and in the past. A family history with a focus on consanguineous parentage, sibling death if any, and details of the affected family members were obtained. Family history was considered positive in case of an affected family member. Treatment details including antimicrobial prophylaxis, intravenous

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A Narrative Review of the Neurological Manifestations of Human Adenosine Deaminase 2 Deficiency

Dzhus,

Ehlers,

Wouters

et al. 2023

J Clin Immunol

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Deficiency of human adenosine deaminase type 2 (DADA2) is a complex systemic autoinflammatory disorder characterized by vasculopathy, immune dysregulation, and hematologic abnormalities. The most notable neurological manifestations of DADA2 are strokes that can manifest with various neurological symptoms and are potentially fatal. However, neurological presentations can be diverse. We here present a review of the neurological manifestations of DADA2 to increase clinical awareness of DADA2 as the underlying diagnosis. We reviewed all published cases of DADA2 from 1 January 2014 until 19 July 2022 found via PubMed. A total of 129 articles describing the clinical features of DADA2 were included in the analysis. Six hundred twenty-eight patients diagnosed with DADA2 were included in the review. 50.3% of patients had at least signs of one reported neurological event, which was the initial or sole manifestation in 5.7% and 0.6%, respectively. 77.5% of patients with neurological manifestations had at least signs of one cerebrovascular accident, with lacunar strokes being the most common and 35.9% of them having multiple stroke episodes. There is a remarkable predilection for the brain stem and deep gray matter, with 37.3% and 41.6% of ischemic strokes, respectively. Other neurological involvement included neuropathies, focal neurological deficits, ophthalmological findings, convulsions, and headaches. In summary, neurological manifestations affect a significant proportion of patients with DADA2, and the phenotype is broad. Neurological manifestations can be the first and single manifestation of DADA2. Therefore, stroke, encephalitis, posterior reversible encephalopathy syndrome, mononeuropathy and polyneuropathy, and Behçet’s disease-like presentations should prompt the neurologist to exclude DADA2, especially but not only in childhood.

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Spectrum of Systemic Auto-Inflammatory Diseases in India: A Multi-Centric Experience

Cited by 13 publications

References 45 publications

Variant in the PLCG2 Gene May Cause a Phenotypic Overlap of APLAID/PLAID: Case Series and Literature Review

Variant in the PLCG2 Gene May Cause a Phenotypic Overlap of APLAID/PLAID: Case Series and Literature Review

Profile of 208 patients with inborn errors of immunity at a tertiary care center in South India

A Narrative Review of the Neurological Manifestations of Human Adenosine Deaminase 2 Deficiency

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