12 results on '"Vijaya Gowri"'
Search Results
2. Lymphoproliferation- a clue towards an underlying monogenic disorder of immune dysregulation- a retrospective analysis from a single center in India
- Author
-
Akshaya Chougule, Vaishnavi Iyengar, Vijaya Gowri, Prasad Taur, Manisha Madkaikar, and Mukesh Desai
- Subjects
Immunology ,Immunology and Allergy - Published
- 2023
3. Monogenic inborn errors of immunity in autoimmune disorders
- Author
-
Iyengar Vaishnavi Venkatachari, Akshaya Chougule, Vijaya Gowri, Prasad Taur, Minnie Bodhanwala, Shakuntala Prabhu, Manisha Madkaikar, and Mukesh Desai
- Subjects
Immunology ,Immunology and Allergy - Published
- 2023
4. Human BCL10 Deficiency due to Homozygosity for a Rare Allele
- Author
-
Lazaro Lorenzo, Jean-Laurent Casanova, Carolina Cubillos-Zapata, Eduardo López-Collazo, Anne Puel, Silvia Sánchez-Ramón, Amin Safa, Rebeca Pérez de Diego, María Vela, Antonio Pérez-Martínez, Mukesh Desai, Maria J. Recio, Ana Van Den Rym, Prasad Taur, Vijaya Gowri, Ambreen Pandrowala, Rubén Martínez-Barricarte, Pablo Gonzalez-Navarro, and Victor Toledano
- Subjects
Male ,0301 basic medicine ,T-Lymphocytes ,T cell ,Immunology ,Chromosome Disorders ,Biology ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Immunology and Allergy ,Lectins, C-Type ,Allele ,Respiratory Tract Infections ,Cells, Cultured ,Immunodeficiency ,B-Lymphocytes ,Mutation ,Homozygote ,Toll-Like Receptors ,Immunologic Deficiency Syndromes ,Infant ,B-Cell CLL-Lymphoma 10 Protein ,medicine.disease ,Phenotype ,BCL10 ,Minor allele frequency ,030104 developmental biology ,medicine.anatomical_structure ,Primary immunodeficiency ,Immunologic Memory ,030215 immunology - Abstract
In 2014, a child with broad combined immunodeficiency (CID) who was homozygous for a private BCL10 allele was reported to have complete inherited human BCL10 deficiency. In the present study, we report a new BCL10 mutation in another child with CID who was homozygous for a BCL10 variant (R88X), previously reported as a rare allele in heterozygosis (minor allele frequency, 0.000003986). The mutant allele was a loss-of-expression and loss-of-function allele. As with the previously reported patient, this patient had complete BCL10 deficiency. The clinical phenotype shared features, such as respiratory infections, but differed from that of the previous patient that he did not develop significant gastroenteritis episodes or chronic colitis. Cellular and immunological phenotypes were similar to those of the previous patient. TLR4, TLR2/6, and Dectin-1 responses were found to depend on BCL10 in fibroblasts, and final maturation of T cell and B cell maturation into memory cells was affected. Autosomal-recessive BCL10 deficiency should therefore be considered in children with CID.
- Published
- 2020
5. Wiskott Aldrich Syndrome: A Multi-Institutional Experience From India
- Author
-
Kohsuke Imai, Pandiarajan Vignesh, Revathi Raj, Harsha Prasada Lashkari, Murugan Sudhakar, Amit Rawat, Ramya Uppuluri, Prasad Taur, Osamu Ohara, Anju Gupta, Prateek Bhatia, Yu-Lung Lau, Vijaya Gowri, Ankur Kumar Jindal, Harish Kumar, Surjit Singh, Koon Wing Chan, Ambreen Pandrowala, Pamela P. Lee, Shigeaki Nonoyama, Rashmi Rikhi, Alka Khadwal, Sagar Bhattad, Jasmina Ahluwalia, Mukesh Desai, Sanjeev Kumar Verma, Manisha Madkaikar, Deepti Suri, Jyoti Sharma, and Anit Kaur
- Subjects
Male ,Pediatrics ,medicine.medical_specialty ,Time Factors ,Wiskott–Aldrich syndrome ,medicine.medical_treatment ,Immunology ,Nonsense mutation ,India ,thrombocytopenia ,Hematopoietic stem cell transplantation ,WASP ,Malignancy ,Risk Assessment ,Disease-Free Survival ,microplatelets ,Risk Factors ,medicine ,Humans ,Immunology and Allergy ,Missense mutation ,Genetic Predisposition to Disease ,Developing Countries ,Original Research ,business.industry ,autoimmunity ,Age Factors ,Hematopoietic Stem Cell Transplantation ,Immunoglobulins, Intravenous ,Infant ,hematopoetic stem cell transplant ,Transplant-Related Mortality ,X-linked thrombocytopenia ,RC581-607 ,bleeding ,medicine.disease ,Wiskott-Aldrich Syndrome ,Phenotype ,Child, Preschool ,Mutation ,Cohort ,Primary immunodeficiency ,Female ,Immunologic diseases. Allergy ,business ,Wiskott-Aldrich Syndrome Protein ,malignancy - Abstract
BackgroundWiskott Aldrich syndrome (WAS) is characterized by bleeding manifestations, recurrent infections, eczema, autoimmunity, and malignancy. Over the last decade, improved awareness and better in-house diagnostic facilities at several centers in India has resulted in increased recognition of WAS. This study reports collated data across major primary immunodeficiency diseases (PID) centers in India that are involved in care of children with WAS and highlights the varied clinical presentations, genetic profile, and outcomes of patients in India.MethodsRequest to share data was sent to multiple centers in India that are involved in care and management of patients with PID. Six centers provided requisite data that were compiled and analyzed.ResultsIn this multi-institutional cohort, clinical details of 108 patients who had a provisional diagnosis of WAS were received. Of these, 95 patients with ‘definite WAS’ were included Fourteen patients were classified as XLT and 81 patients as WAS. Median age at onset of symptoms of patients was 3 months (IQR 1.6, 6.0 months) and median age at diagnosis was 12 months (IQR 6,48 months). Clinical profile included bleeding episodes (92.6%), infections (84.2%), eczema (78.9%), various autoimmune manifestations (40%), and malignancy (2.1%). DNA analysis revealed 47 variants in 67 cases. Nonsense and missense variants were the most common (28.4% each), followed by small deletions (19.4%), and splice site defects (16.4%). We also report 24 novel variants, most of these being frameshift and nonsense mutations resulting in premature termination of protein synthesis. Prophylactic intravenous immunoglobulin (IVIg) was initiated in 52 patients (54.7%). Hematopoietic stem cell transplantation (HSCT) was carried out in 25 patients (26.3%). Of those transplanted, disease-free survival was seen in 15 patients (60%). Transplant related mortality was 36%. Outcome details were available for 89 patients. Of these, 37% had died till the time of this analysis. Median duration of follow-up was 36 months (range 2 weeks- 12 years; IQR 16.2 months- 70 months).ConclusionsWe report the first nationwide cohort of patients with WAS from India. Bleeding episodes and infections are common manifestations. Mortality continues to be high as curative therapy is not accessible to most of our patients.
- Published
- 2021
6. The Spectrum of Clinical, Immunological, and Molecular Findings in Familial Hemophagocytic Lymphohistiocytosis: Experience From India
- Author
-
Amruta Dhawale, Pallavi Gaikwad, Ramya Uppuluri, Snehal Shabrish, Swati Kanakia, Meena Sivasankaran, Ambreen Pandrowala, Dharani Jayaraman, Pranoti Kini, Abhilasha Sampagar, Deenadayalan Munirathnam, Sneha Sawant-Desai, Mukesh Desai, Aparna Dalvi, Shweta Shinde, Brijesh Arora, Pandiarajan Vignesh, Aaqib Zaffar Banday, Madhura Kelkar, Meenakshi Girish, Manisha Madkaikar, Jahnavi Aluri, Santanu Sen, Amit Rawat, Gouri Hule, Narendra K Chaudhary, Ramprasad Vedam, R Yadav, Nayana Nambiar, Umair Ahmed Bargir, Revathi Raj, Vijaya Gowri, Farah Jijina, Priyanka Setia, Neha Jodhawat, Manasi Kulkarni, M. R. Lokeshwar, Abhijit Chaudhary, S. Chandrakla, Priyanka Kambli, Ratna Sharma, Nitin Shah, Prasad Taur, Maya Gupta, Ujjal Poddar, and Amita Aggarwal
- Subjects
Male ,lcsh:Immunologic diseases. Allergy ,Immunology ,India ,medicine.disease_cause ,Lymphohistiocytosis, Hemophagocytic ,familial hemophagocytic lymphohistocytosis ,T-Lymphocyte Subsets ,Databases, Genetic ,medicine ,Humans ,Immunology and Allergy ,Genetic Predisposition to Disease ,UNC13D ,HLH-targeted therapy ,Child ,flow cytomertry ,Alleles ,perforin ,Original Research ,degranulation ,Hemophagocytic lymphohistiocytosis ,biology ,Genetic heterogeneity ,business.industry ,Computational Biology ,Disease Management ,Infant ,Familial Hemophagocytic Lymphohistiocytosis ,Immune dysregulation ,medicine.disease ,Combined Modality Therapy ,Phenotype ,Treatment Outcome ,Perforin ,STX11 ,Child, Preschool ,NGS ,Mutation ,biology.protein ,Female ,Cytokine secretion ,Disease Susceptibility ,lcsh:RC581-607 ,business ,Biomarkers - Abstract
Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of immune dysregulation characterized by hyperactivation of the immune system, excessive cytokine secretion and severe systemic inflammation. HLH is classified as familial (FHL) when associated with mutations in PRF1, UNC13D, STX11, and STXBP2 genes. There is limited information available about the clinical and mutational spectrum of FHL patients in Indian population. This study is a retrospective analysis of 101 molecularly characterized FHL patients over the last 10 years from 20 different referral centers in India. FHL2 and FHL3 together accounted for 84% of cases of FHL in our cohort. Patients belonging to different FHL subtypes were indistinguishable based on clinical and biochemical parameters. However, flow cytometry-based assays viz. perforin expression and degranulation assay were found to be specific and sensitive in diagnosis and classification of FHL patients. Molecular characterization of respective genes revealed 76 different disease-causing mutations including 39 (51%) novel mutations in PRF1, UNC13D, STX11, and STXBP2 genes. Overall, survival was poor (28%) irrespective of the age of onset or the type of mutation in our cohort. Altogether, this article sheds light on the current scenario of FHL in India. Our data reveal a wide genetic heterogeneity of FHL in the Indian population and confirms the poor prognosis of FHL. This study also emphasizes that though mutational analysis is important for diagnostic confirmation of FHL, flow cytometry based assays help significantly in rapid diagnosis and functional validation of novel variants identified.
- Published
- 2021
7. Clinical, Immunological, and Molecular Features of Severe Combined Immune Deficiency: A Multi-Institutional Experience From India
- Author
-
Prasad Taur, Manisha Madkaikar, Kirti Gupta, Madhubala Sharma, Deepti Suri, Johnson Nameirakpam, Anit Kaur, Alka Khadwal, Aparna Dalvi, Sagar Bhattad, Anjani Gummadi, Sreejesh Sreedharanunni, Michael S. Hershfield, Ranjana W. Minz, Sandip Bartakke, Tamaki Kato, Biman Saikia, Deenadayalan Munirathnam, Komal Singh, Harsha Prasada Lashkari, Fouzia Na, Amita Aggarwal, Raghuram Cp, Ramya Uppuluri, Ankit Mehta, Yu-Lung Lau, Ankita Singh, Neha Jodhawat, Surjit Singh, Revathi Raj, Stalin Ramprakash, Mukesh Desai, Yumi Ogura, Koon Wing Chan, Amit Rawat, Kaushal Sharma, Vijaya Gowri, Aruna Rajendran, Ankur Kumar Jindal, Ananthvikas Jayaram, Daniel Leung, Biju George, Rajni Kumrah, Shigeaki Nonoyama, Priyanka Kambli, Sarath Balaji, Kohsuke Imai, Pandiarajan Vignesh, Osamu Ohara, Anju Gupta, Ambreen Pandrowala, and Meena Sivasankaran
- Subjects
lcsh:Immunologic diseases. Allergy ,Male ,2019-20 coronavirus outbreak ,Pediatrics ,medicine.medical_specialty ,DCLRE1C ,medicine.medical_treatment ,Immunology ,India ,Hematopoietic stem cell transplantation ,Immune system ,medicine ,Humans ,Immunology and Allergy ,BCG ,Original Research ,Newborn screening ,newborn screening ,business.industry ,Infant ,medicine.disease ,Early infancy ,hematopoietic stem cell transplantation ,severe combined immune deficiency ,Primary immunodeficiency ,Female ,Severe Combined Immunodeficiency ,Age of onset ,lcsh:RC581-607 ,business - Abstract
BackgroundSevere Combined Immune Deficiency (SCID) is an inherited defect in lymphocyte development and function that results in life-threatening opportunistic infections in early infancy. Data on SCID from developing countries are scarce.ObjectiveTo describe clinical and laboratory features of SCID diagnosed at immunology centers across India.MethodsA detailed case proforma in an Excel format was prepared by one of the authors (PV) and was sent to centers in India that care for patients with primary immunodeficiency diseases. We collated clinical, laboratory, and molecular details of patients with clinical profile suggestive of SCID and their outcomes. Twelve (12) centers provided necessary details which were then compiled and analyzed. Diagnosis of SCID/combined immune deficiency (CID) was based on 2018 European Society for Immunodeficiencies working definition for SCID.ResultsWe obtained data on 277 children; 254 were categorized as SCID and 23 as CID. Male-female ratio was 196:81. Median (inter-quartile range) age of onset of clinical symptoms and diagnosis was 2.5 months (1, 5) and 5 months (3.5, 8), respectively. Molecular diagnosis was obtained in 162 patients - IL2RG (36), RAG1 (26), ADA (19), RAG2 (17), JAK3 (15), DCLRE1C (13), IL7RA (9), PNP (3), RFXAP (3), CIITA (2), RFXANK (2), NHEJ1 (2), CD3E (2), CD3D (2), RFX5 (2), ZAP70 (2), STK4 (1), CORO1A (1), STIM1 (1), PRKDC (1), AK2 (1), DOCK2 (1), and SP100 (1). Only 23 children (8.3%) received hematopoietic stem cell transplantation (HSCT). Of these, 11 are doing well post-HSCT. Mortality was recorded in 210 children (75.8%).ConclusionWe document an exponential rise in number of cases diagnosed to have SCID over the last 10 years, probably as a result of increasing awareness and improvement in diagnostic facilities at various centers in India. We suspect that these numbers are just the tip of the iceberg. Majority of patients with SCID in India are probably not being recognized and diagnosed at present. Newborn screening for SCID is the need of the hour. Easy access to pediatric HSCT services would ensure that these patients are offered HSCT at an early age.
- Published
- 2021
8. Clinical and Genetic Profile of X-Linked Agammaglobulinemia: A Multicenter Experience From India
- Author
-
Vijaya Gowri, Rajni Sharma, Osamu Ohara, Shigeaki Nonoyama, Ananthvikas Jayaram, Jitendra Kumar Shandilya, Biman Saikia, Anju Gupta, Pamela P. Lee, Sneha Sawant-Desai, Revathi Raj, Ambreen Pandrowala, Sanjib Mondal, Harsha Prasad Lashkari, Amit Rawat, Prasad Taur, Kanika Arora, Aparna Dalvi, Rahul Tyagi, Deenadayalan Munirathnam, Anuj Shukla, Manisha Madkaikar, Yu-Lung Lau, Ankur Kumar Jindal, Mukesh Desai, Ramya Uppuluri, Manas Kalra, Maya Gupta, Vibhu Joshi, Liza Rajasekhar, Sagar Bhattad, Deepti Suri, Kohsuke Imai, Ravinder Garg, Pandiarajan Vignesh, Amita Aggarwal, Koon Wing Chan, Ruchi Saka, Aaqib Zaffar Banday, Madhubala Sharma, Surjit Singh, and Ranjana W. Minz
- Subjects
Male ,0301 basic medicine ,lcsh:Immunologic diseases. Allergy ,medicine.medical_specialty ,X-linked agammaglobulinemia ,Immunology ,India ,Neutropenia ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,Agammaglobulinemia ,Internal medicine ,hemic and lymphatic diseases ,intravenous immunoglobulin ,Streptococcus pneumoniae ,Agammaglobulinaemia Tyrosine Kinase ,Humans ,Immunology and Allergy ,Medicine ,neutropenia ,Child ,BTK gene ,Original Research ,Bronchiectasis ,business.industry ,Genetic Variation ,Immunoglobulins, Intravenous ,Infant ,Genetic Diseases, X-Linked ,Exons ,Genetic Profile ,Protein-Tyrosine Kinases ,medicine.disease ,030104 developmental biology ,Otitis ,arthritis ,Child, Preschool ,Primary immunodeficiency ,Female ,medicine.symptom ,business ,lcsh:RC581-607 ,Meningitis ,030217 neurology & neurosurgery ,Encephalitis - Abstract
BackgroundThere is paucity of literature on XLA from developing countries. Herein we report the clinical and molecular profile and outcome in a multicenter cohort of patients with XLA from India.MethodsData on XLA from all regional centers supported by the Foundation for Primary Immunodeficiency Diseases (FPID), USA and other institutions providing care to patients with PIDs were collated. Diagnosis of XLA was based on European Society for Immunodeficiencies (ESID) criteria.ResultsWe received clinical details of 195 patients with a provisional diagnosis of XLA from 12 centers. At final analysis, 145 patients were included (137 ‘definite XLA’ and eight ‘probable/possible XLA’). Median age at onset of symptoms was 12.0 (6.0, 36.0) months and median age at diagnosis was 60.0 (31.5, 108) months. Pneumonia was the commonest clinical manifestation (82.6%) followed by otitis media (50%) and diarrhea (42%). Arthritis was seen in 26% patients while 23% patients developed meningitis. Bronchiectasis was seen in 10% and encephalitis (likely viral) in 4.8% patients. Pseudomonas aeruginosa was the commonest bacterial pathogen identified followed by Streptococcus pneumoniae, Staphylococcus aureus and Klebsiella pneumoniae. Molecular analysis revealed 86 variants in 105 unrelated cases. Missense variants in BTK gene were the most common (36%) followed by frameshift (22%) and nonsense variants (21%). Most pathogenic gene variants (53%) were clustered in the distal part of gene encompassing exons 14–19 encoding for the tyrosine kinase domain. Follow-up details were available for 108 patients. Of these, 12% had died till the time of this analysis. The 5-year and 10-year survival was 89.9% and 86.9% respectively. Median duration of follow-up was 61 months and total duration of follow-up was 6083.2 patient-months. All patients received intravenous immunoglobulin (IVIg) replacement therapy. However, in many patients IVIg could not be given at recommended doses or intervals due to difficulties in accessing this therapy because of financial reasons and lack of universal health insurance in India. Hematopoietic stem cell transplant was carried out in four (2.8%) patients.ConclusionThere was a significant delay in the diagnosis and facilities for molecular diagnosis were not available at many centers. Optimal immunoglobulin replacement is still a challenge
- Published
- 2021
9. Clinical and Genetic Spectrum of a Large Cohort of Patients With Leukocyte Adhesion Deficiency Type 1 and 3: A Multicentric Study From India
- Author
-
Priyanka Setia, Revathi Raj, Shiv Prasad Mundada, Amita Agarwal, Himanshi Chaudhary, Umair Ahmed Bargir, Deenadayalan Munirathnam, Harsha Prasad Lashkari, Vibhu Joshi, Sandeep Nemani, Sheela Nampoothiri, Amruta Dhawale, Sagar Bhattad, Vidya Krishna, Pallavi Gaikwad, Ramya Uppuluri, Ruchi Nanavati, Mamta Manglani, Shweta Shinde, Indumathi Ck, Prasad Taur, Madhubala Sharma, Kanika Arora, Parinitha Gutha, Anju Gupta, Vijaya Gowri, Ananthvikas Jayaram, Manas Kalra, Madhura Kelkar, Anupam Sachdeva, Vinod Gornale, Rakesh Kumar Pilania, Stalin Ramprakash, Maya Gupta, Gouri Hule, Mukesh Desai, Geeta Madathil Govindraj, Swati Kanakia, Manisha Madkaikar, Ambreen Pandrowala, Priyanka Kambli, Amit Rawat, Avinash Sharma, Sunil Karande, Abhilasha Sampagar, Meena Sivasankaran, Shobita Katiyar, Girish Subramanyam, Neha Jodhawat, Aparna Dalvi, Sarath Balaji, Sneha Sawant-Desai, R Yadav, Nayana Nambiar, and Raghuram Cp
- Subjects
Male ,lcsh:Immunologic diseases. Allergy ,Pathology ,medicine.medical_specialty ,Adolescent ,Leukocytosis ,Neutrophils ,Leukocyte-Adhesion Deficiency Syndrome ,Immunology ,India ,CD18 ,ITGβ2 ,Umbilical cord ,Sepsis ,Leukocyte Adhesion Deficiency Type 1 ,Cohort Studies ,symbols.namesake ,medicine ,Cell Adhesion ,Leukocytes ,Immunology and Allergy ,Humans ,Child ,Immunodeficiency ,Leukocyte adhesion deficiency ,Original Research ,FERMT3 ,Sanger sequencing ,business.industry ,Infant, Newborn ,Infant ,Membrane Proteins ,medicine.disease ,Otitis ,medicine.anatomical_structure ,CD18 Antigens ,Child, Preschool ,Mutation ,symbols ,Female ,medicine.symptom ,CD11 ,business ,lcsh:RC581-607 ,Leukocyte Adhesion deficiency - Abstract
Leukocyte adhesion deficiency (LAD) syndrome is a group of inborn errors of immunity characterized by a defect in the cascade of the activation and adhesion leading to the failure of leukocyte to migrate to the site of tissue injury. Three different types of LAD have been described. The most common subtype is LAD type 1 (LAD1) caused due to defects in theITGβ2gene. LAD type 2 (LAD2) is caused by mutations in theSLC35C1gene leading to a generalized loss of expression of fucosylated glycans on the cell surface and LAD type 3 (LAD3) is caused by mutations in theFERMT3gene resulting in platelet function defects along with immunodeficiency. There is a paucity of data available from India on LAD syndromes. The present study is a retrospective analysis of patients with LAD collated from 28 different centers across India. For LAD1, the diagnosis was based on clinical features and flow cytometric expression of CD18 on peripheral blood leukocytes and molecular confirmation by Sanger sequencing. For patients with LAD3 diagnosis was largely based on clinical manifestations and identification of the pathogenic mutation in theFERMT3gene by next-generation Sequencing. Of the total 132 cases diagnosed with LAD, 127 were LAD1 and 5 were LAD3. The majority of our patients (83%) had CD18 expression less than 2% on neutrophils (LAD1°) and presented within the first three months of life with omphalitis, skin and soft tissue infections, delayed umbilical cord detachment, otitis media, and sepsis. The patients with CD18 expression of more than 30% (LAD1+) presented later in life with skin ulcers being the commonest manifestation. Bleeding manifestations were common in patients with LAD3. Persistent neutrophilic leukocytosis was the characteristic finding in all patients. 35 novel mutations were detected in theITGβ2gene, and 4 novel mutations were detected in theFERMT3gene. The study thus presents one of the largest cohorts of patients from India with LAD, focusing on clinical features, immunological characteristics, and molecular spectrum.
- Published
- 2020
10. Clinical and Molecular Findings in Mendelian Susceptibility to Mycobacterial Diseases: Experience From India
- Author
-
Prasad D. Taur, Vijaya Gowri, Ambreen Abdulwahab Pandrowala, Vaishnavi V. Iyengar, Akshaya Chougule, Zainab Golwala, Shraddha Chandak, Reepa Agarwal, Purva Keni, Neha Dighe, Minnie Bodhanwala, Shakuntala Prabhu, Biju George, N. A. Fouzia, Eunice Sindhuvi Edison, Arun Kumar Arunachalam, Manisha Rajan Madkaikar, Aparna Dhondi Dalvi, Reetika Malik Yadav, Umair Ahmed Bargir, Priyanka Madhav Kambli, Amit Rawat, Jhumki Das, Vibhu Joshi, Rakesh Kumar Pilania, Ankur Kumar Jindal, Sunil Bhat, Sagar Bhattad, Jeeson Unni, Nita Radhakrishnan, Revathi Raj, Ramya Uppuluri, Shivani Patel, Harsha Prasada Lashkari, Amita Aggarwal, Manas Kalra, Zarir Udwadia, Vibha Sanjay Bafna, Tarun Kanade, Anne Puel, Jacinta Bustamante, Jean Laurent Casanova, and Mukesh M. Desai
- Subjects
lcsh:Immunologic diseases. Allergy ,Adult ,Male ,Salmonella ,Adolescent ,Immunology ,India ,BCG-osis ,medicine.disease_cause ,Young Adult ,IL-12/IL-23/ISG15/IFN-γ axis ,Immunity ,Histoplasma ,medicine ,Immunology and Allergy ,Humans ,Genetic Predisposition to Disease ,Child ,Retrospective Studies ,Original Research ,Mycobacterium Infections ,GeneXpert MTB/RIF ,biology ,business.industry ,Coinfection ,Infant, Newborn ,Receptors, Interleukin-12 ,Infant ,Retrospective cohort study ,biology.organism_classification ,Immunity, Innate ,Vaccination ,Phenotype ,Mycobacterium tuberculosis complex ,intracellular pathogens ,anti-tubercular treatment ,Child, Preschool ,Mutation ,BCG Vaccine ,IL-12Rβ1 defect ,Female ,lcsh:RC581-607 ,business ,Mycobacterium - Abstract
Mendelian Susceptibility to Mycobacterial diseases (MSMD) are a group of innate immune defects with more than 17 genes and 32 clinical phenotypes identified. Defects in the IFN-γ mediated immunity lead to an increased susceptibility to intracellular pathogens like mycobacteria including attenuated Mycobacterium bovis-Bacillus Calmette-Guérin (BCG) vaccine strains and non-tuberculous environmental mycobacteria (NTM), Salmonella, fungi, parasites like Leishmania and some viruses, in otherwise healthy individuals. Mutations in the IL12RB1 gene are the commonest genetic defects identified. This retrospective study reports the clinical, immunological, and molecular characteristics of a cohort of 55 MSMD patients from 10 centers across India. Mycobacterial infection was confirmed by GeneXpert, Histopathology, and acid fast bacilli staining. Immunological workup included lymphocyte subset analysis, Nitro blue tetrazolium (NBT) test, immunoglobulin levels, and flow-cytometric evaluation of the IFN-γ mediated immunity. Genetic analysis was done by next generation sequencing (NGS). Disseminated BCG-osis was the commonest presenting manifestation (82%) with a median age of presentation of 6 months due to the practice of BCG vaccination at birth. This was followed by infection with Salmonella and non-typhi Salmonella (13%), Cytomegalovirus (CMV) (11%), Candida (7%), NTM (4%), and Histoplasma (2%). Thirty-six percent of patients in cohort were infected by more than one organism. This study is the largest cohort of MSMD patients reported from India to the best of our knowledge and we highlight the importance of work up for IL-12/IL-23/ISG15/IFN-γ circuit in all patients with BCG-osis and suspected MSMD irrespective of age.
- Published
- 2020
11. Spectrum of Systemic Auto-Inflammatory Diseases in India: A Multi-Centric Experience
- Author
-
Prasad Taur, Rajni Kumrah, Deepti Suri, Anju Gupta, Amit Rawat, Biju George, Amita Aggarwal, Ambreen Pandrowala, Ankur Kumar Jindal, Pandiarajan Vignesh, Kanika Arora, Marco Gottorno, Adriana Almeida de Jesus, Vibhu Joshi, Rakesh Kumar Pilania, Michael S. Hershfield, Sagar Bhattad, Mukesh Desai, Raphaela Goldbach-Mansky, Isabella Ceccherini, Vijaya Gowri, Surjit Singh, Gummadi Anjani, Shubha R. Phadke, Fouzia N. Aboobacker, Swati Kanakia, and Eunice Sindhuvi Edison
- Subjects
lcsh:Immunologic diseases. Allergy ,0301 basic medicine ,Male ,medicine.medical_specialty ,Immunology ,Familial Mediterranean fever ,India ,medicine.disease_cause ,Pyrin domain ,03 medical and health sciences ,0302 clinical medicine ,NOMID/CINCA ,deficiency of adenosine deaminase 2 ,inflammasome ,Internal medicine ,medicine ,Immunology and Allergy ,Humans ,Type I interferonopathies ,Stomatitis ,systemic autoinflamatory diseases ,Original Research ,030203 arthritis & rheumatology ,Mevalonate kinase deficiency ,business.industry ,Hyper-IgD syndrome ,Hereditary Autoinflammatory Diseases ,Immune dysregulation ,medicine.disease ,Pharyngitis ,030104 developmental biology ,Cohort ,hyper IgD syndrome ,A20 (TNFAIP3) ,Female ,medicine.symptom ,lcsh:RC581-607 ,business - Abstract
Background: Systemic autoinflammatory diseases (SAID) are rare inherited disorders involving genes regulating innate immune signaling and are characterized by periodic or chronic multi-systemic inflammation.Objective: To describe spectrum of clinical, immunological, molecular features, and outcomes of patients with SAID in India.Methods: Request to share data was sent to multiple centers in India that are involved in care and management of patients with Inborn Errors of Immunity. Six centers provided requisite data that were compiled and analyzed.Results: Data on 107 patients with SAID were collated—of these, 29 patients were excluded due to unavailability of complete information. Twelve patients (15%) had type 1 interferonopathies, 21 (26%) had diseases affecting inflammasomes, 30 patients (41%) had non-inflammasome related conditions and 1five patients (19%) had Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis (PFAPA). Type1 interferonopathies identified in the cohort included patients with Deficiency of Adenosine Deaminase 2 (DADA2) (six patients; five families); STING-associated vasculopathy infantile-onset (SAVI) (three patients, one family); Spondyloenchondro-dysplasia with Immune Dysregulation (SPENCD) (two patients). Diseases affecting inflammasomes include Mevalonate Kinase Deficiency (eight patients); Cryopyrin-Associated Periodic Syndromes (CAPS) (seven patients); NLR Family, Pyrin domain-containing 12 (NLRP12) (two patients); Familial Mediterranean fever (FMF) (two patients); Autoinflammation and PLCG2-associated antibody deficiency and immune dysregulation (APLAID) (two patients). TNF receptor-associated periodic syndrome (TRAPS) (three patients); A20 haploinsufficiency (four patients); Deficiency of Interleukin 1 Receptor Antagonist (DIRA) (two patients) were categorized as non-inflammasome related conditions. There were significant delays in diagnosis Corticosteroids and other immunosuppressive agents were used for treatment as anti-IL-1 drugs and other biological agents were and still are not available in India. Eight (16.3%) patients had so far succumbed to their illness.Conclusions: This is the first nationwide cohort of patients with SAID from India. Clinical manifestations were diverse. Overlapping of clinical features with other relatively common rheumatological disorders often resulted in delays in diagnosis. More nationwide efforts are needed to enhance awareness of SAID among health care professionals and there is an urgent need to make targeted immunotherapies universally available.
- Published
- 2020
12. Clinical Profile of Hyper-IgE Syndrome in India
- Author
-
Venkateswaran Vellaichamy Swaminathan, Revathi Raj, Manas Kalra, Ramya Uppuluri, Amit Rawat, Harsha Prasada Lashkari, Aparna Dalvi, Gladys Cyril, Mukesh Desai, Sagar Bhattad, Adil Karim, Reetika Mallik Yadav, Anuj Shukla, Ranjana W. Minz, Ankur Kumar Jindal, Smrity Sahu, Vijaya Gowri, Harish Kumar, Biman Saikia, Geeta Madathil Govindaraj, Surjit Singh, Ambreen Pandrowala, Manisha Madkaikar, Prasad Taur, Vignesh Pandiarajan, and Deepti Suri
- Subjects
lcsh:Immunologic diseases. Allergy ,Adult ,Male ,STAT3 Transcription Factor ,medicine.medical_specialty ,Retained primary teeth ,Adolescent ,Immunology ,Eczema ,India ,STAT3 LOF ,Immunoglobulin E ,Cohort Studies ,Exon ,hyper-IgE syndrome ,medicine ,Immunology and Allergy ,Humans ,Multicenter Studies as Topic ,Craniofacial ,Child ,Skin ,Original Research ,biology ,business.industry ,Infant ,rare variants ,Recurrent fractures ,medicine.disease ,Dermatology ,Indian subcontinent ,Pneumonia ,Child, Preschool ,Mutation ,multi-centric study ,biology.protein ,Female ,lcsh:RC581-607 ,DOCK8 Deficiency ,business ,Job Syndrome - Abstract
Introduction:Hyper-IgE Syndrome (HIES) is a rare inborn error of immunity (IEI) characterized by a constellation of symptoms related to susceptibility toStaphylococcalskin and pulmonary infections, eczema, raised serum IgE (>2,000 IU/ml), craniofacial anomalies, and recurrent bone fractures. Data on HIES from the Indian subcontinent is scarce and restricted to small case series and case reports. This is the first compilation of national data on HIES.Materials and Methods:A total 103 cases clinically diagnosed and treated as HIES were analyzed from nine centers. Cases with clinical and/or molecular diagnosis of DOCK8 deficiency were not included. Patients were divided into two groups: group I for whom a heterozygous rare variant of STAT3 was identified, and group II, with clinical features similar to those of AD STAT3 deficiency, but without any genetic diagnosis.Results:Genetic diagnosis was available in 27 patients (26.2%) and all harbored rare variants in the STAT3 gene. Majority of these STAT3 HIES patients presented with recurrent skin abscesses (77.7%) or pneumonia (62.9%) or both (59.2%). Other features included eczema (37%), candidiasis (55.5%), facial dysmorphism (55.5%), recurrent fractures (11.1%), and retained primary teeth (7.4%).Mycobacterialinfections were seen in a significant 18.5%. Mortality was seen in three subjects (11.1%). A similar trend in the clinical presentation was observed when all the 103 patients were analyzed together. Twenty percent of patients without a rare variant in the STAT3 gene had an NIH score of ≥40, whereas, 51.9% of STAT3 HIES subjects had scores below the cut off of ≥40. TH17 cell numbers were low in 10/11 (90.9%) STAT3 HIES tested. Rare variants observed were 8 in exon 21; 8 in exon 13; 3 in exon 10; 2 in exon 15, and one each in exon 6, 16, 17, 19, 22, and splice site downstream of exon 12. Seven variants were novel and included F174S, N567D, L404Sfs*8, G419 =, M329K, T714I, R518X, and a splice site variant downstream of exon 12.Conclusions:The report includes seven novel STAT3 variants, including a rare linker domain nonsense variant and a CC domain variant.Mycobacterialdiseases were more frequent, compared to western literature.
- Published
- 2020
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.