Publications by authors named "Harikrishnan Gangadharan"

8 Publications

  • Page 1 of 1

A Rare Cause of Double Negative αβ T Cell Lymphocytosis.

Indian J Hematol Blood Transfus 2021 Jul 12;37(3):511-513. Epub 2020 Nov 12.

Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.

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http://dx.doi.org/10.1007/s12288-020-01381-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239097PMC
July 2021

A Rare Cause of Ortner's Syndrome and a Case-Based Review of Literature.

Indian J Otolaryngol Head Neck Surg 2021 Apr 1:1-4. Epub 2021 Apr 1.

Department of General Medicine, Government Medical College, Kottayam, Kerala, India.

Ortner's syndrome refers to the compression of the recurrent laryngeal nerve by cardiovascular disorders of various etiologies. We describe a rare case of Ortner's syndrome caused by thoracic aorta aneurysm and a brief review of literature on this unusual cause of Ortner's syndrome. Hoarseness of voice due to the compression of recurrent laryngeal nerve by thoracic aorta aneurysm could be a harbinger of aneurysmal rupture.
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http://dx.doi.org/10.1007/s12070-021-02521-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013204PMC
April 2021

Polymorphism of genes involved in methotrexate pathway: Predictors of response to methotrexate therapy in Indian rheumatoid arthritis patients.

Int J Rheum Dis 2021 May 29;24(5):654-662. Epub 2021 Mar 29.

Department of Clinical Immunology & Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.

Introduction: The adenosine pathway is one of the ways through which methotrexate (MTX) ameliorates inflammation. We therefore explored an association of polymorphism of genes involved in adenosine and MTX metabolic pathways with response to MTX.

Methods: Association of polymorphism in 7 genes (rs2236225 [MTHFD1 1958G>A], rs17602729 [AMPD1 G>A], rs1127354 [ITPA C>A], rs1431131 [TGFBR2 A>T], rs2372536 [ATIC C>G], rs11188513 [ENTPD1 C>T] and rs5751876 [ADORA2A T>C]) with efficacy of MTX was studied in Indian rheumatoid arthritis (RA) patients. The patients, classified by European League Against Rheumatology (EULAR)/American College of Rheumatology (ACR) 2010 criteria, were DMARD (disease-modifying antirheumatic drug)-naïve, with Disease Activity Score (DAS28) >3.2. After 4 months of MTX monotherapy, patients were classified as responders (R) or non-responders (NR) based on EULAR response criteria. Genotyping was done by TaqMan 5' nuclease assay and association of gene polymorphisms with response to MTX was determined by Chi-squared test.

Results: Two hundred and twenty-six patients (86% female, median age 40 [interquartile range, IQR = 17.25] years), with disease duration of 24 (IQR = 38.25) months and DAS28-C-reactive protein score of 4.61 (IQR = 1.34) were enrolled. After therapy, 186 patients were classified as R and 40 as NR. GG genotype of ATIC (P = .01, odds ratio [OR] 2.56, 95% CI, 1.04-6.30) and CC genotype of ITPA (P = .009, OR 1.34, 95% CI 1.02-1.76) genes were found to be associated with the response. On binary logistic regression analysis, GG genotype of ATIC and CC of ITPA genes were independent predictors of the response.

Conclusion: Polymorphisms of ATIC and ITPA genes alone or with clinical variables were associated with response to MTX therapy in Indian RA patients.
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http://dx.doi.org/10.1111/1756-185X.14100DOI Listing
May 2021

Monogenic Lupus with IgA Nephropathy Caused by Spondyloenchondrodysplasia with Immune Dysregulation.

Indian J Pediatr 2021 08 13;88(8):819-823. Epub 2021 Mar 13.

Department of Medical Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.

Monogenic disorders causing systemic lupus erythematosus represent a small subset of cases. Type-1 interferonopathies, like spondyloenchondrodysplasia with immune dysregulation constitute an important functional category of monogenic lupus. Apart from autoimmune disorders, neurological and skeletal abnormalities are additional manifestations observed in this disorder. A young female presented with seizures due to acute hemorrhagic stroke secondary to malignant hypertension. On evaluating the cause for hypertension, there was evidence of glomerulonephritis and multiple autoantibodies positivity including dsDNA. A diagnosis of lupus was made based on clinical and laboratory findings. Kidney biopsy revealed mesangial proliferative glomerulonephritis with predominant IgA deposits favouring IgA nephropathy. Additional features in the form of short stature with vertebral abnormalities and bilateral basal ganglia calcification led to evaluation of Type-1 interferonopathies. Sanger sequencing identified a novel compound heterozygous variants c.550C>T (p.Q184*) in exon 3 and c.740T>G (p.L247R) in exon 4 of ACP5 gene. Parents were found to be carriers of the variants in ACP5 gene. Management included antihypertensive agents and symptomatic therapy. On follow-up, there was complete resolution of glomerulonephritis and normalization of blood pressure. This case report documents the classic phenotype comprising autoimmune, skeletal, and neurological abnormalities in spondyloenchondrodysplasia with immune dysregulation with a novel variant on Sanger sequencing in an Indian patient. This report also highlights the rare coexistence of IgA nephropathy in monogenic lupus.
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http://dx.doi.org/10.1007/s12098-020-03636-xDOI Listing
August 2021

Adenosine Deaminase Gene Polymorphism and Baseline Serum Level of Adenosine Deaminase as a Biomarker of Response to Methotrexate in Rheumatoid Arthritis.

J Clin Rheumatol 2021 Dec;27(8):e609-e611

From the Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.

Background: Methotrexate (MTX) is the first-line therapy for rheumatoid arthritis (RA), but nearly 30% of RA patients do not respond to it. Methotrexate acts by enhancing the level of adenosine, which gets converted to inosine by the enzyme adenosine deaminase (ADA). We studied whether ADA gene polymorphism and serum levels of total ADA are associated with responsiveness to MTX.

Methods: Two hundred seven disease-modifying antirheumatic drug-naive active RA patients (DAS28-ESR [Disease Activity Score-28 for rheumatoid arthritis with erythrocyte sedimentation rate] ≥3.2) satisfying the European League Against Rheumatism (EULAR)/American College of Rheumatology 2010 criteria were enrolled. Genotyping was done in all patients, and in a subset (n = 59), blood was collected at baseline and at 2 months of MTX treatment for serum total ADA estimation by ELISA. Response at 4 months was assessed by EULAR criteria, and patients were classified as responders or nonresponders. The correlation of baseline clinical parameters, ADA gene polymorphism, and serum total ADA levels with EULAR response was sought.

Results: After 4 months of MTX monotherapy, 172 patients (83.1%) were classified as responders and 35 (16.9%) as nonresponders. Except DAS28-ESR (6.1 [5.43-6.84] in responders vs 5.6 [4.77-6.21] in nonresponders, p = 0.02), other baseline parameters (age, disease duration, ESR, and C-reactive protein level) were similar between responders and nonresponders. Single nucleotide polymorphisms in ADA gene, baseline serum ADA levels (10.52 ± 5.37 ng/mL in responders vs 12.28 ± 5.14 ng/mL in nonresponders), or change in ADA levels after 2 months of MTX therapy did not show any association with MTX response (p = 0.73, p = 0.34, p = 0.55, respectively). Adenosine deaminase genotype did not affect the blood ADA level.

Conclusions: No association was seen between ADA single nucleotide polymorphism rs244076 as well as serum ADA level and response to MTX therapy.
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http://dx.doi.org/10.1097/RHU.0000000000001594DOI Listing
December 2021

Clinical Sequencing Solves a Diagnostic Dilemma by Identifying a Novel Pathogenic Variant in USB1 Gene Causing Poikiloderma with Neutropenia.

Indian J Pediatr 2021 03 16;88(3):270-271. Epub 2020 Sep 16.

Department of Clinical Immunology & Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.

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http://dx.doi.org/10.1007/s12098-020-03502-wDOI Listing
March 2021

Insights into the knowledge, attitude and practices for the treatment of idiopathic inflammatory myopathy from a cross-sectional cohort survey of physicians.

Rheumatol Int 2020 Dec 2;40(12):2047-2055. Epub 2020 Sep 2.

Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, India.

The idiopathic inflammatory myopathies (IIM) are heterogeneous and lead to high morbidity and mortality. Knowledge deficits among healthcare professionals could be detrimental to clinical care. Identifying areas of deficient Knowledge, Attitude and Practice (KAP) of IIM can improve physician education and patient outcomes. To assess the proportion of physicians treating IIM with poor KAP and identify the key areas of deficit. An anonymised and validated e-survey (57 questions) was circulated among physicians treating IIM (purposive sampling). Responses were evaluated using the Likert scale for good (> 70% correct response), poor (> 20% chose > 2 answers) and the rest as intermediate consensus. Descriptive statistics were used. Intergroup comparisons were done using non-parametric tests. Of 80 (9.1% of 883) respondents, 90% were rheumatologists and 37.5% academicians. The knowledge base of treating physicians was good in specific domains such as triggers (80-90%), clinical presentation (MDA5, statin myositis, steroid myopathy, anti-synthetase syndrome) (82-92%), IIM mimics (41-89%), investigations (23-92%) and risk of osteoporosis in IIM (79%). There is also an intermediate knowledge base/consensus for outcome measures (30-56%) and response criteria (30-53%). There was poor knowledge and consensus on trials (27-34%), EULAR/ACR criteria (31%) and exercise-based interventions (17-62%). While 90% agree on the need for muscle biopsy to diagnose polymyositis, only one-third advocated it for juvenile and adult DM. Physicians have a good understanding of the triggers, clinical presentation and mimics of IIM. Poor to intermediate knowledge and consensus exists regarding muscle biopsy, outcome measures, response criteria and exercise-based interventions, which could be addressed through future focussed educational initiatives.
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http://dx.doi.org/10.1007/s00296-020-04695-1DOI Listing
December 2020

Multiple jeopardy: Diagnostic and therapeutic challenges in vasculitic flare.

Int J Rheum Dis 2020 May 7;23(5):697-701. Epub 2020 Apr 7.

Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow, India.

A 57-year old gentleman had presented a year back with inflammatory oligoarthritis and vasculitic neuropathy, diagnosed as unclassifiable vasculitis, initiated on oral corticosteroids and intravenous cyclophosphamide (monthly X 6). His disease stabilized and he had been maintained on azathioprine, which had to be stopped due to acute pancreatitis with subsequent pseudocyst formation, requiring percutaneous drainage suspecting infection. Within a week of pseudocyst drainage, he developed sudden onset pain in left upper limb, with absent left upper limb pulses, loss of motor function of left hand, myocardial ischemia, and extensive thrombosis of the left upper limb arteries. Neuropathy in the left upper limb was either vasculitic, or ischemic due to arterial thrombosis. However, multifocal thrombosis suggested an ongoing vasculitic flare. In view of possible infected pancreatic pseudocyst, intravenous methylprednisolone pulse was contra-indicated. Hence, he was offered intravenous immunoglobulin (IVIG) therapy, despite the risk of potentially worsening the prevalent prothrombotic state. On the second day of IVIG, he developed transiently tingling and weakness of right hand with vasculitic rashes, which subsequently resolved, reaffirming the suspicion of vasculitic flare. After completing IVIG therapy, the weakness in his left hand had markedly improved. His myocardial ischemia had also recovered, with a repeat echocardiography showing normalization of prior left ventricular hypokinesia. In the intervening period, the pseudocysts were drained, following which he was initiated on rituximab. This case highlights numerous challenges in the initial diagnosis, distinguishing vasculitic from ischemic neuropathy, and the management of vasculitic flare during infection.
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http://dx.doi.org/10.1111/1756-185X.13836DOI Listing
May 2020
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