Publications by authors named "Dolly Daniel"

35 Publications

Breast milk contains red cell isohaemagglutinins: An observational study of 176 mothers.

Vox Sang 2022 Jun 26;117(6):847-852. Epub 2022 Jan 26.

Department of Transfusion Medicine and Immunohaematology, Christian Medical College, Vellore, India.

Background And Objectives: Maternal antibodies are transferred to the child, predominantly IgG, via the transplacental route, and mostly IgA through breast milk. Cases reported by us and others have shown the transfer of red cell allo-antibodies through breast milk. This study was conducted to assess the presence of isohaemagglutinins in breast milk, the range of titres, and the correlation between breast milk and maternal plasma titres.

Materials And Methods: A total of 176 mothers were recruited in this study. Breast milk was collected after sufficient feeding was established and within 2-5 days of delivery in a sterile container without any anticoagulant. Antibody screen, identification and titres were performed on maternal plasma as well as breast milk.

Results: Anti-A and anti-B in breast milk corresponding to their respective maternal blood groups were found in all the samples. This study has shown titres in the breast milk of anti-A and anti-B ranging from 2 to 1024 in both saline and Coombs phases. There was no association between plasma and breast milk titres, thus making it impossible to predict which mother may potentially transfer a larger amount of these haemagglutinins. Isotypes of anti-A and anti-B were evaluated in both plasma and breast milk of 11 samples, which showed predominantly IgG in 7 (63.63%) and predominantly IgA in 4 (36.36%) samples.

Conclusion: Our study demonstrates the presence of a wide range of titres for IgG antibodies of the ABO blood group system in breast milk. The clinical impact of this finding needs to be studied further, as it assumes great relevance in developing countries where anaemia continues to challenge young infants.
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http://dx.doi.org/10.1111/vox.13253DOI Listing
June 2022

Factors associated with mortality among moderate and severe patients with COVID-19 in India: a secondary analysis of a randomised controlled trial.

BMJ Open 2021 10 4;11(10):e050571. Epub 2021 Oct 4.

Infectious Diseases, Kasturba Hospital for Infectious Diseases, Mumbai, Maharashtra, India.

Objective: Large data on the clinical characteristics and outcome of COVID-19 in the Indian population are scarce. We analysed the factors associated with mortality in a cohort of moderately and severely ill patients with COVID-19 enrolled in a randomised trial on convalescent plasma.

Design: Secondary analysis of data from a Phase II, Open Label, Randomized Controlled Trial to Assess the Safety and Efficacy of Convalescent Plasma to Limit COVID-19 Associated Complications in Moderate Disease.

Setting: 39 public and private hospitals across India during the study period from 22 April to 14 July 2020.

Participants: Of the 464 patients recruited, two were lost to follow-up, nine withdrew consent and two patients did not receive the intervention after randomisation. The cohort of 451 participants with known outcome at 28 days was analysed.

Primary Outcome Measure: Factors associated with all-cause mortality at 28 days after enrolment.

Results: The mean (SD) age was 51±12.4 years; 76.7% were males. Admission Sequential Organ Failure Assessment score was 2.4±1.1. Non-invasive ventilation, invasive ventilation and vasopressor therapy were required in 98.9%, 8.4% and 4.0%, respectively. The 28-day mortality was 14.4%. Median time from symptom onset to hospital admission was similar in survivors (4 days; IQR 3-7) and non-survivors (4 days; IQR 3-6). Patients with two or more comorbidities had 2.25 (95% CI 1.18 to 4.29, p=0.014) times risk of death. When compared with survivors, admission interleukin-6 levels were higher (p<0.001) in non-survivors and increased further on day 3. On multivariable Fine and Gray model, severity of illness (subdistribution HR 1.22, 95% CI 1.11 to 1.35, p<0.001), PaO/FiO ratio <100 (3.47, 1.64-7.37, p=0.001), neutrophil lymphocyte ratio >10 (9.97, 3.65-27.13, p<0.001), D-dimer >1.0 mg/L (2.50, 1.14-5.48, p=0.022), ferritin ≥500 ng/mL (2.67, 1.44-4.96, p=0.002) and lactate dehydrogenase ≥450 IU/L (2.96, 1.60-5.45, p=0.001) were significantly associated with death.

Conclusion: In this cohort of moderately and severely ill patients with COVID-19, severity of illness, underlying comorbidities and elevated levels of inflammatory markers were significantly associated with death.

Trial Registration Number: CTRI/2020/04/024775.
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http://dx.doi.org/10.1136/bmjopen-2021-050571DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8491003PMC
October 2021

Laboratory and clinical comparison of the efficacy of prestorage leukoreduction of red cells at cold versus room temperature.

Transfusion 2021 09 25;61(9):2556-2565. Epub 2021 Jun 25.

Department of Transfusion Medicine and Immunohaematology, Christian Medical College, Vellore, India.

Background: The temperature at which filtration takes place has been reported to influence the efficacy of leukoreduction. We aimed to compare the residual leukocyte count (RLC) in red cell units (RCUs) filtered at cold (CT) versus room temperature (RT) and to assess whether this correlates clinically with a difference in the incidence of acute transfusion reactions (ATRs).

Methods And Materials: In the first part of the study, whole blood units collected were randomly allocated for subsequent filtration at CT and RT, respectively. RLC postfiltration was assessed using flow cytometry. The second part of the study was a nonrandomized clinical trial in which incidence of ATR was compared between RCUs filtered at RT and CT for 6 months each.

Results: Thirty-five RCUs each underwent leukofiltration at CT and RT, respectively. The median RLCs in the filtered units at CT and RT were 0.02 × 10 and 0.1 × 10 leukocytes/unit, respectively (p = .0001), with no difference in red blood cell (RBC) recovery (p = .41). During the second part, 3455 RCUs filtered at RT and 3539 RCUs filtered at CT were transfused to patients. The rate of febrile non-hemolytic transfusion reaction (FNHTR) among transfused patients was less with units filtered at CT (1 per 2000 transfusions) in comparison to RT (1 per 588 transfusions). The difference was, however, not significant (p = .14).

Conclusion: If change in temperature alone can cause significant reduction in leukocytes, then it is a simple way to curtail the rate of this common yet unpleasant reaction and reduce the reaction rate at minimal cost.
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http://dx.doi.org/10.1111/trf.16570DOI Listing
September 2021

Derivation of Clinical-Grade Induced Pluripotent Stem Cell Lines from Erythroid Progenitor Cells in Xenofree Conditions.

Methods Mol Biol 2022 ;2454:775-789

Centre for Stem Cell Research (A Unit of inStem, Bengaluru), Christian Medical College, Vellore, India.

One of the major hurdles in realizing the therapeutic potential of human-induced pluripotent stem cells (iPSC) is the generation of clinical-grade iPSC lines and their differentiated progenies for preclinical and clinical applications. Therefore, there is a need to have standardized protocols for efficient generation of clinical-grade iPSC lines from easily accessible somatic cells in feeder-free, xenofree GMP grade culture conditions without genomic integration of the reprogramming factors. Here, we provide a detailed protocol for expansion of erythroid progenitor cells from peripheral blood mononuclear cells (PBMNC) and generation of iPSC lines in feeder-free and xenofree culture conditions from these cells by using GMP grade reagents. With this optimized protocol, clinical-grade iPSC lines can be derived from erythroid progenitor cells expanded from peripheral blood, which is easy-to-access, minimally invasive, and can be obtained from any donors. It will have implications in developing a large number of iPSC lines from individual healthy donors, diseased patients, or donors with homozygous human leukocyte antigen (HLA) for "haplobanking."
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http://dx.doi.org/10.1007/7651_2021_349DOI Listing
January 2022

Trophic effects of multiple administration of mesenchymal stem cells in children with osteogenesis imperfecta.

Clin Transl Med 2021 04;11(4):e385

Department of Paediatric Orthopaedics, Christian Medical College, Vellore, Tamil Nadu, India.

The safety of mesenchymal stem cell therapy for osteogenesis imperfecta has been demonstrated previously. However, it is unknown how the trophic effects are mediated by stem cells. In the present commentary, we bring to the attention of readers the recent report by Infante et al in the journal of clinical and translational medicine. The TERCELOI clinical trial presented the possible paracrine effect of transplanted MSCs in vitro and in vivo using proteomics and transcriptomic analysis. This novel finding adds new knowledge in the field of regenerative medicine. However, the scarcity of solid evidence in growth warrants a more thorough discussion.
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http://dx.doi.org/10.1002/ctm2.385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019582PMC
April 2021

Prevalence of HLA-B*27 subtypes in the Tamil population of India with Ankylosing spondylitis and its correlation with clinical features.

Hum Immunol 2021 Jun 24;82(6):404-408. Epub 2021 Mar 24.

Department of Transfusion Medicine and Immunohaematology, Christian Medical College, Vellore, India.

Introduction: HLA-B*27 is strongly associated with Ankylosing spondylitis (AS). Its subtypes show considerable geographic and ethnic difference. The main aim of this study was to assess the frequency of subtypes of HLA-B*27 in the Indian Tamil AS patients.

Methods And Materials: Adult AS patients positive for HLA-B*27 were considered for the study. The high-resolution typing to define HLA-B*27 subtypes were done using Invitrogen B kits from One Lambda (SeCore® Sequencing Kits, Thermo Fisher, United States).

Results And Conclusion: Prevalence of subtypes identified were HLA-B*27:04 (52.2%), HLA-B*27:05 (41.6%), HLA-B*27:07 (3.5%) and HLA-B*27:02 (2.7%). All subtypes showed disease predisposition for males. The most common extra articular manifestation seen was enthesitis in HLA-B*27:04 and HLA-B*27:05. Uveitis was mainly associated with HLA-B*27:05 and dactylitis with HLA-B*27:04. A significant peripheral joints involvement for female and axial joint involvement for males was seen in HLA-B*27:04. Our study establishes the prevalence of HLA-B*27 subtypes and the associated clinical phenotypes among the Indian Tamil population. Considering the variability of presentation, organ involvement, and disease course in different subtypes and across ethnicities it is critical to define these associations in the ethnic populations we treat for their appropriate care considering the significant negative health and socioeconomic effects of AS.
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http://dx.doi.org/10.1016/j.humimm.2021.03.001DOI Listing
June 2021

Autoantibodies Among HIV-1 Infected Individuals and the Effect of Anti-Retroviral Therapy (ART) on It.

Curr HIV Res 2021 ;19(3):277-285

Department of Clinical Virology, Christian Medical College, Vellore, Tamil Nadu, 632004, India.

Background: Antiretroviral therapy (ART) has led to a decline in autoimmune diseases but lacks studies on its effect on autoantibodies.

Methods: It is a cross-sectional study with archived samples from 100 paired HIV-1 infected ART naïve and experienced individuals and 100 prospectively collected matched blood-donor controls. Antinuclear antibody, IgG anticardiolipin antibody, IgM and IgG β2 glycoprotein-1 antibodies, and total IgG levels were detected. Results are expressed as mean with standard deviation (SD), median, percentage positivity, and a p<0.05 is considered significant. The study was approved by the Institutional Review Board.

Results: The median viral load of the treatment naïve samples was 4.34 Log copies/mL, while all were virally suppressed post ART with a median duration of treatment for 12 months (range: 3-36 months). The percentage of antinuclear antibody positivity was 5% among ART naïve and controls, with a decrease of 2% post ART (p= 0.441). The positivity for anti-cardiolipin antibody was 15% among ART naïve while none of the ART experienced or controls were positive (p<0.05). IgM β2 glycoprotein-1 were 4%, 1% and 3% among ART naïve, treated and controls, respectively (p<0.05). IgG β2 glycoprotein-1 was 2% among ART naïve while none of the treated and controls were positive (p<0.05). The mean total IgG level among ART naïve, experienced, and controls were 21.82 (SD 6.67), 16.91 (SD 3.38), 13.70 (SD 2.24) grams/Litre, respectively (p<0.05).

Conclusion: ART has a significant effect on IgG anti-cardiolipin antibody and total IgG but only a marginal effect on ANA, IgM, and IgG β2 glycoprotein-1 antibodies.
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http://dx.doi.org/10.2174/1570162X19666210217120337DOI Listing
November 2021

Impact of rituximab on the T-cell flow cytometric crossmatch.

Transpl Immunol 2021 02 22;64:101360. Epub 2020 Dec 22.

Department of Transfusion medicine & Immunohaematology, Christian Medical College, Vellore, Tamil Nadu, India. Electronic address:

Rituximab is frequently used in the setting of ABO-incompatible renal transplants, and highly sensitized patients. Its interference with B-cell flow cytometric crossmatch (B-FCXM) is well known. However, its effect on the T-cell flow cytometric crossmatch (T-FCXM) has not been described. We aimed to evaluate the effect of rituximab on the T-FCXM using non-pronase and pronase treated donor lymphocytes and compare results with the single antigen bead (SAB) assay. In this retrospective study, 28 patients on rituximab therapy were evaluated against 30 donors. Using non-pronase treated donor lymphocytes, all 30 FCXMs showed strong B-cell positivity {median (IQR) B-cell ratio: 184.65 (253.17)} which significantly reduced {1.0 (1.18); p < 0.00001} with pronase treatment. 'T-cell tailing' phenomenon was observed in 17/30 FCXMs in the non-pronase group as a 'tail of T-cells', indicating a rare sub-population. However, it disappeared in the pronase-treated group. SAB assay did not show donor-specific antibodies (DSA) in all 17 patients with 'T-cell tailing' phenomenon. Although, rituximab is described to impact only B-FCXM, we have consistently found 'T-cell tailing' in 57% of T-FCXMs, which clears with pronase treatment. The 'T-cell tailing' led to weak positive T-FCMX ratios due to increased MFI in the FL1 channel. However, the absence of DSA in all recipients reinforces the fact that this is a false positive finding and should not be misconstrued as a possible class I DSA. Structural homology of Fc receptors on activated T-cells to CD20 could be a possible explanation of the same and provide insight into a novel mechanism of action of rituximab.
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http://dx.doi.org/10.1016/j.trim.2020.101360DOI Listing
February 2021

The challenge of using the virtual crossmatch as a singular tool for the detection of Anti-HLA antibodies- A study from a tertiary care institute from South India.

Transpl Immunol 2021 04 28;65:101349. Epub 2020 Oct 28.

Department of Transfusion Medicine and Immunohaematology, Christian Medical College, Vellore 632004, Tamil Nadu, India. Electronic address:

Introduction: Detection of donor specific antibodies (DSA) is critical in both solid organ and mismatched haematopoietic stem cell transplants. The single antigen bead assay (SAB) is widely used as a virtual crossmatch in these settings. However, HLA allele variation across ethnicities and differing genetic backgrounds is a well-known and acknowledged fact and representation of alleles prevalent in a population is key while using a virtual crossmatch as a sole decision making tool. Against this background, this study was performed to assess the feasibility of using the SAB as a single tool to identify DSA in our population.

Materials And Methods: The HLA alleles identified in the study population were analysed to assess their representation on SAB panels from two different vendors.

Results: The study population comprised of a total of 966 subjects for whom 6 loci high resolution HLA typing was done. A total of 241 different alleles were assigned in the population. Among the 241 alleles identified in our study population, 48.55% (n = 117) alleles were represented in the SAB A panel and 48.13% (n = 116) represented in the SAB B panel. Unrepresented alleles were 51.45% (n = 124) in panel A and 51.87% (n = 125) in panel B. All the twelve alleles were represented for 16.05% (n = 155) and 16.25% (n = 157) of study population in panel A and in panel B respectively. The remaining individuals (83.95%, (n = 811) in panel A and 83.75%, (n = 809) in panel B) had at least one allele unrepresented.

Conclusion: Our study addresses an important limitation in utilizing the SAB as a single tool to identify DSA, owing to non-representation of locally prevalent / unique alleles in our population. More than 50% of alleles were unrepresented in both the SAB assays we studied, which included alleles from both Class I and Class II. We recommend therefore that, until a comprehensive coverage of alleles is provided, or epitope matching becomes robust, that the SAB be combined with a physical crossmatch when mismatched alleles are not represented.
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http://dx.doi.org/10.1016/j.trim.2020.101349DOI Listing
April 2021

Association of prior sensitizing events with anti-human leukocyte antigen antibodies: An analysis of renal transplant recipients in a tertiary care centre in South India.

Transfus Apher Sci 2020 Aug 13;59(4):102808. Epub 2020 May 13.

Department of Transfusion Medicine and Immunohaematology, 5th Floor, ASHA Building, Christian Medical College, Vellore, Tamil Nadu, India.

Traditionally, sensitizing events such as previous pregnancies, previous transfusions and prior transplants result in the production of anti-Human Leukocyte Antigen (HLA) antibodies. However, it has been observed that, anti-HLA antibodies have been detected in many patients with no prior history of sensitizing events. This retrospective study analysed the most recent 100 consecutive Single Antigen Bead (SAB) assay results performed on 100 patients. The SAB assay is used routinely to detect anti-HLA antibodies in transplant recipients. Results of the SAB assay were analyzed and subsequently studied to see if a correlation existed between sensitizing events, the type of events and presence of antibody. Analysis showed that 77% (77/100) had anti-HLA antibodies. 61 out of 100 patients had prior sensitizing events while the remaining 39 had none. Both these groups showed an almost equal percent of patients with anti-HLA antibodies 77% (47/61) and 76.9% (30/39) respectively. A single sensitizing event was seen in 54.1% (33/61) patients including previous transfusions in 29.5% (18/61), pregnancies in 11.4% (7/61) and prior transplant in 13.1% (8/61). Our study suggests that irrespective of whether patients have prior sensitizing events or not, patients run the risks of alloimmunization, and therefore appropriate screening tests should be included in the pre-transplant compatibility algorithm.
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http://dx.doi.org/10.1016/j.transci.2020.102808DOI Listing
August 2020

Frequency of Platelet Crossmatch Positivity and Predictive Value for Poor Platelet Increment Among Paediatric Oncohaematology Patients in India.

Indian J Hematol Blood Transfus 2020 Jan 25;36(1):164-170. Epub 2019 Sep 25.

1Department of Transfusion Medicine and Immunohaematology, Christian Medical College, Vellore, Tamil Nadu 632004 India.

Immune platelet destruction is a significant cause for platelet refractoriness. The platelet crossmatch-a solid phase red cell adherence assay utilizes donor platelets and patient serum to assess compatibility and appears to be a feasible option in resource constrained settings. This study was done to evaluate the frequency of platelet crossmatch positivity among Paediatric Oncohaematology patients and also to assess whether a positive crossmatch is predictive of unsuccessful platelet transfusions in this group of patients. Paediatric Oncohaematology patients who received platelet transfusions between March 2013 and September 2013 were included in the study. The pre-transfusion patient sample and a segment from the transfused donor unit were used for performing the platelet crossmatch. A blood sample was collected one hour after the transfusion to assess post-transfusion platelet count. Corrected count increment (CCI) was calculated using the standard formula. CCI ≤ 7500/µL/m/10 was considered evidence of an unsuccessful transfusion. Seventy-three platelet crossmatches were performed for 69 patients, of which 30 patient samples (41%) showed crossmatch positivity. 25 (89.2%) of 28 unsuccessful transfusions showed crossmatch positivity, and 40 (88.9%) of 45 successful transfusions showed negative crossmatches ( = 0.03). Crossmatch positivity among transfusion dependent Paediatric Oncohaematology patients was as high as 42%, when ABO matched platelet units were allocated without further testing. Our results indicate that this test may be a reliable tool to select compatible platelet units and an effective intervention in the management of patients at risk of immune platelet refractoriness.
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http://dx.doi.org/10.1007/s12288-019-01193-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042467PMC
January 2020

Do red cell alloantibodies continue to challenge breast fed babies?

Transfus Med 2020 Aug 21;30(4):281-286. Epub 2020 Feb 21.

Department of Transfusion Medicine and Immunohaematology, Christian Medical College, Vellore, India.

Background: Newborns have limited specific immune capability at birth, owing to delayed and constrained development of adaptive immunity. To supplement this period the mother passively transfers antibodies to the child either transplacentally or through breast milk. When maternal alloimmunisation occurs through foreign or fetal red cell surface antigens, stimulating the production of immunoglobulin G (IgG) antibodies, these IgG antibodies can cross the placenta and cause haemolytic disease of the fetus and the newborn.

Objective: We present two case reports of a neonate and an infant in whom IgG red cell alloantibodies were transferred through maternal breast milk.

Methods: Maternal serum, baby's serum and expressed breast milk samples were tested for the presence of red cell alloantibodies using gel card. Antibody screening, antibody identifications and titres alongside monospecific direct antiglobulin test, IgG subtypes were performed using the standard methods.

Results: In the first case, a 6-month-old child was incidentally found to have positive antibody screen. Anti-KELL1 was identified, which was also present in maternal serum and breast milk. The second neonate was evaluated for haemolysis and was found to have anti-D. Anti-D was also detected in the maternal serum and breast milk. Both babies did not have any sensitising events. The first baby was asymptomatic, but the second baby had ongoing haemolysis until 1 month.

Conclusion: We report that maternal anti-KELL1 and anti-D antibodies were present in breast milk and were capable of being transferred to a feeding child. Our case report also raises interesting and unanswered immunologic fundamentals that should be considered in neonates with unexplained anaemia or delayed and persistent haemolysis.
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http://dx.doi.org/10.1111/tme.12672DOI Listing
August 2020

Association between human leukocyte antigen-DRB1 and human leukocyte antigen-DQB1 alleles and pemphigus vulgaris in Indian patients: A case-control study.

Indian J Dermatol Venereol Leprol 2018 May-Jun;84(3):280-284

Department of Biostatistics, Christian Medical College, Vellore, Tamil Nadu, India.

Background: HLA-DRB1*04, -DRB1*08, -DRB1*14, -DQB1*03 and -DQB1*05 are reported to have significant association with pemphigus vulgaris; however, this is partially dependent on ethnicity. This study was done to determine the HLA-DR and -DQ types prevalent in Indian patients with pemphigus vulgaris.

Methods: A prospective case-control study was done for a period of 9 months in Christian Medical College Vellore, India. HLA typing was done by PCR-SSOP method in 50 cases and 50 healthy controls. Allele frequencies in cases and controls were compared and odds ratios with 95% confidence interval were calculated.

Results: The mean age of the patients (29 females, 21 males) and that of controls (36 males, 14 females) were 41.3 ± 13.65 and 35.42 ± 11.09 years, respectively. HLA-DRB1*14 was present in 47 patients and 18 controls (OR, 27.85; 95% CI, 7.57-102.42) and HLA-DQB1*05 was seen in 47 patients and 24 controls (OR, 16.97; 95% CI, 4.66-61.80). The haplotype DRB1*14, DQB1*05 was present in 44 patients and 14 controls (OR, 18.86; 95% CI, 6.58-54.05). DRB1*15 was present in 7 cases and 16 controls (OR, 0.35; 95% CI, 0.13-0.94) and DQB1*06 was present in 8 cases and 19 controls (OR, 0.31; 95% CI, 0.12-0.80). HLA-DQB1*03 was associated with significantly higher pemphigus disease area index scores.

Limitations: The main limitations were that the numbers studied were small as the study was conducted at a single center, and the haplotype analysis was limited only to the proband. PDAI scores could have been influenced by prior treatment.

Conclusion: There was a significant association between HLA-DRB1*14 and HLA-DQB1*05 and pemphigus vulgaris in our patients. A negative association was seen with DRB1*15 and DQB1*06.
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http://dx.doi.org/10.4103/ijdvl.IJDVL_1014_16DOI Listing
September 2018

Prevalence of Adult Celiac Disease in India: Regional Variations and Associations.

Am J Gastroenterol 2016 Jan 5;111(1):115-23. Epub 2016 Jan 5.

Department of Gastrointestinal Sciences, Christian Medical College, Vellore, India.

Objectives: Although celiac disease (CeD) affects 1% of people in the northern part of India, it is believed to be uncommon in the southern and northeastern parts because of significant differences in dietary pattern and ethnicity. We estimated the prevalence of CeD in these three populations. In a subset, we also investigated differences in the prevalence of HLA-DQ 2/8 allelotype and dietary grain consumption.

Methods: A total of 23,331 healthy adults were sampled from three regions of India-northern (n=6207), northeastern (n=8149), and southern (n=8973)-and screened for CeD using IgA anti-tissue transglutaminase antibody. Positive tests were reconfirmed using a second ELISA. CeD was diagnosed if the second test was positive and these participants were further investigated. A subsample of participants was tested for HLA-DQ2/-DQ8 and underwent detailed dietary evaluation.

Results: Age-adjusted prevalence of celiac autoantibodies was 1.23% in northern, 0.87% in northeastern, and 0.10% in southern India (P<0.0001). Prevalence of CeD and latent CeD, respectively, was 8.53/1,000 and 3.70/1,000 in northern, 4.66/1,000 and 3.92/1,000 in northeastern, and 0.11/1,000 and 1.22/1,000 in the southern part. The population prevalence of genes determining HLA-DQ2 and/or -DQ8 expression was 38.1% in northern, 31.4% in northeastern, and 36.4% in southern India. Mean daily wheat intake was highest in northern (455 g) compared with northeastern (37 g) or southern part (25 g), whereas daily rice intake showed an inverse pattern.

Conclusions: CeD and latent CeD were most prevalent in northern India and were the least in southern India. The prevalence correlated with wheat intake and did not reflect differences in the genetic background.
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http://dx.doi.org/10.1038/ajg.2015.398DOI Listing
January 2016

Scrub Typhus Seroprevalence in Healthy Indian Population.

J Clin Diagn Res 2015 Oct 1;9(10):DM01-2. Epub 2015 Oct 1.

Professor, Department of Clinical Microbiology, Christian Medical College , Vellore, India .

Scrub typhus, a zoonosis caused by Orientia tsutsugamushi, is an important cause of acute febrile illness in India. This preliminary study determines the seroprevalence of scrub typhus in healthy Indian adults by measuring IgM and IgG antibodies to scrub typhus by ELISA in 100 healthy blood donors. Our study demonstrates a 15% seroprevalence of scrub typhus in adults. Further studies are needed to confirm these findings especially in children.
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http://dx.doi.org/10.7860/JCDR/2015/14708.6623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4625242PMC
October 2015

Clinical profile of childhood-onset psoriasis and prevalence of HLA-Cw6: a hospital-based study from India.

Postgrad Med J 2015 Jun 6;91(1076):309-14. Epub 2015 May 6.

Department of Medicine, Christian Medical College and Hospital, Vellore, Tamil Nadu, India.

Background: Childhood-onset psoriasis (COP), a distinct clinical entity, may be associated with HLA-Cw6 positivity and metabolic and cardiovascular complications. There is some evidence that HLA-Cw6 positivity is associated with more extensive or severe disease and that positivity is lower in Asian patients than in Caucasians. We describe the clinical profile, prevalence of the HLA-Cw6 allele, metabolic syndrome (MetS) and vitamin D deficiency in Indian patients with COP.

Methods: In this cross-sectional hospital-based study over 15 months (June 2010-August 2011), 108 consecutive patients with disease onset ≤16 years were enrolled. Demographic, clinical and laboratory data were collected. Patients were categorised as children with COP (CCOP; n=69) or adults with COP (ACOP; n=39). Disease severity was assessed using body surface area (BSA) involved and Psoriasis Area and Severity Index (PASI) score.

Results: The most common morphological type was chronic plaque psoriasis; follicular psoriasis was seen only in children. Adults with disease onset in childhood, when compared with CCOP, had later disease onset (11.0±4.0 vs 6.9±3.8 (mean±SD) years; p<0.0001) of greater severity (p=0.021) based on BSA involved. PASI scores were, however, similar in ACOP and CCOP. Body mass index was not associated with disease severity. Of the 83 who underwent HLA-C typing, 46 (55.4%) were positive; positivity was associated with guttate lesions (p=0.031), scalp involvement (p=0.004), greater BSA involvement (p=0.002) and higher PASI scores (p=0.013). Vitamin D deficiency, obesity and MetS were present in 77.4%, 10.7% and 14.5% of patients, respectively.

Conclusions: Among Indian patients, CCOP have earlier disease onset than ACOP. HLA-Cw6 was associated with guttate psoriasis, scalp involvement and disease severity. Vitamin D deficiency was common.
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http://dx.doi.org/10.1136/postgradmedj-2014-133188DOI Listing
June 2015

Red cell alloimmunization among antenatal women attending a tertiary care hospital in south India.

Indian J Med Res 2013 ;138:68-71

Department of Transfusion Medicine & Immunohaematology, Christian Medical College & Hospital, Vellore, India.

Background & Objectives: Detection of maternal alloimmunization against red cell antigens is vital in the management of haemolytic disease of the foetus and newborn (HDFN). This study was conducted to measure the presence of allosensitization to blood group antibodies in the antenatal women attending a tertiary care hospital and to observe the proportion of minor blood group antibodies to assess the benefit of screening for the same.

Methods: All antenatal women registered in the hospital between January 2008 and January 2009, were screened for irregular antibodies using a commercial 3-cell antibody screening panel. Antibody identification was performed on samples found positive using a commercial 11 cell-panel.

Results: Screening was performed on 5347 women, 339 (6.34%) of whom were Rh negative. Allosensitization was found in 79 women (1.48%; confidence interval 1.17 -1.84). In 29 of these 79 (37%) women the allo-antibodies could not be identified. In the remaining 50 women, 54 antibodies were characterized. A total of 40 clinically significant antibody specificities were identified among 36 women, of whom four were Rh(D) positive. Allosensitization with clinically significant antibodies was found in 9.43 per cent (confidence interval 6.55-13.06) Rh(D) negative and in 0.08 per cent (confidence interval .02-0.2) Rh(D) positive women. Anti D was the most frequent antibody found in 8.85 per cent Rh(D) negative women. The remaining clinically significant antibodies identified included anti-C, c, E, Jk(a), Jk(b), M and S. In Rh(D) negative women, anti-D and antibodies of the Rh system contributed 83.3 and 94.4 per cent of clinically significant antibodies. However, in Rh(D) positive women, non-Rh antibodies comprised three out of four clinically significant antibodies.

Interpretation & Conclusions: The presence of alloimmunization in our study corroborated with data reported from India. The most frequent antibody was anti-D. However, a significant fraction was non-D. Alloimmunization among Rh(D) positive women though low as compared to Rh(D) negative women, included clinically significant antibodies, and most of these were non Rh.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3767264PMC
April 2014

Perspectives and attitudes to voluntary blood donation in a tertiary referral hospital blood bank.

Asian J Transfus Sci 2013 Jul;7(2):158-9

Department of Transfusion Medicine and Immunohaematology, John Scudder Memorial Blood Bank, Christian Medical College, Vellore - 632 004, Tamilnadu, India.

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http://dx.doi.org/10.4103/0973-6247.115589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3757781PMC
July 2013

Ahead to 100% of voluntary nonremunerated blood donation at a tertiary referral hospital blood bank in South India.

Asian J Transfus Sci 2012 Jul;6(2):190

Department Transfusion Medicine and Immunohaematology, John Scudder Memorial Blood Bank, Christian Medical College, Vellore, Tamilnadu, India.

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http://dx.doi.org/10.4103/0973-6247.98954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3439765PMC
July 2012

How deceased donor transplantation is impacting a decline in commercial transplantation-the Tamil Nadu experience.

Transplantation 2012 Apr;93(8):757-60

Department of Nephrology, Madras Medical Mission, Chennai, Tamil Nadu, India.

India with a population of 1.2 billion has a renal transplantation rate of 3.25 per million population. The major cause of chronic kidney disease is hypertension and diabetes. The crude and age-adjusted incidence rates of end-stage renal disease are estimated to be 151 and 232 per million population, respectively, in India. There was a remarkable lack of knowledge in the public about deceased organ donation until a decade ago. However, the role played by the media and nongovernmental organizations in partnership with the government has emphasized and implemented deceased donor transplantation in certain states in India-to mention particularly, the Tamil Nadu model. In the last 2 years, deceased organ donation has reached 1.3 per million population in Tamil Nadu, thereby effectively eliminating commercial transplantation. There is no religious bar for organ donation. A central transplant coordinator appointed by the government oversees legitimate and transparent allocation of deceased organs both in the public and private facilities as per the transplant waiting list. This model also takes care of the poor sections of society by conducting donation and transplantation through government-run public facilities free of cost. In the last 2 years, deceased donor transplantation has been performed through this network procuring organs such as the heart, heart valves, lung, liver, kidneys, cornea, and skin. The infrastructural lack of immunological surveillance-including donor-specific antibody monitoring, human leukocyte antigen typing, and panel reactive antibody except in a few tertiary care centers-prevents allocation according to the immunological status of the recipient. This private-public partnership promoting deceased donor transplantation has effectively eliminated commercialization in transplantation in the state of Tamil Nadu with a population of 72 million which is a model for other regions of South Asia and developing countries.
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http://dx.doi.org/10.1097/TP.0b013e3182469b91DOI Listing
April 2012

Bioscavenger therapy for organophosphate poisoning - an open-labeled pilot randomized trial comparing fresh frozen plasma or albumin with saline in acute organophosphate poisoning in humans.

Clin Toxicol (Phila) 2010 Oct 6;48(8):813-9. Epub 2010 Oct 6.

Medical Intensive Care Unit, Christian Medical College & Hospital, Ida Scudder Road, Vellore 632 004, Tamil Nadu, India.

Introduction: Traditional treatment of organophosphate poisoning (OP) with oximes has had limited success. Fresh frozen plasma (FFP) or albumin, acting as bioscavengers to mop up free organophosphate, has been recently proposed as a treatment modality. In this pilot open-label, three-arm, randomized controlled study exploring proof of concept, we evaluated if bioscavenger therapy had a role in OP.

Patients And Methods: Sixty patients with significant poisoning presenting within 12 hours, with suppression of pseudocholinesterase activity to < 1,000 U/L, were randomized to receive FFP (8 bags, 250 mL each over 3 days), 20% human albumin (4 × 100 mL over 3 days), or saline (2,000 mL over 3 days) in addition to atropine and supportive care. Pseudocholinesterase and organophosphate levels were measured pretreatment, post-infusion (Day 2, Day 3), and predischarge and expressed as mean ± standard error. The incidence of intermediate syndrome, need for mechanical ventilation, atropine requirement, and mortality were assessed.

Results: Twenty patients received albumin and 19 patients each FFP or saline. FFP increased pseudocholinesterase levels (250 ± 44-1,241 ± 364 U/L) significantly (p = 0.007). Small, nonsignificant increases were observed with saline (160 ± 30-259 ± 78) and albumin (146 ± 18-220 ± 61). Organophosphate levels reduced in all 3 arms; no clear-cut trends were observed. We observed more cases of intermediate syndrome with FFP [10/19 (53%) vs. 5/20 (25%) vs. 5/19 (26%), FFP, albumin, and saline arms (p = 0.15)]. The interventions did not affect ventilatory requirements (14/19 vs. 15/20 vs. 14/19) or prevent delayed intubation. There were no differences in mean (±standard error) atropine requirement (in milligrams) in the first 3 days (536 ± 132 vs. 361 ± 125 vs. 789 ± 334) and duration (in days) of ventilation (10.0 ± 2.1 vs. 7.1 ± 1.5 vs. 7.5 ± 1.5) or hospital stay (12.4 ± 2.2 vs. 9.8 ± 1.4 vs. 9.8 ± 1.6). Two patients developed adverse effects with FFP. Mortality was similar (4/19 vs. 5/20 vs. 2/19, p = 0.6).

Conclusions: Despite significant increase in pseudocholinesterase levels with FFP, this pilot study did not demonstrate favorable trends in clinical outcomes with FFP or albumin.
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http://dx.doi.org/10.3109/15563650.2010.518970DOI Listing
October 2010

Accuracy and clinical usefulness of the CoaguChek S and XS Point of Care devices when starting warfarin in a hospital outreach setting.

Thromb Res 2009 Apr 29;123(6):909-13. Epub 2008 Nov 29.

Flinders Medical Centre, Department of Haematology, Bedford Park, South Australia 5042.

Objective: To assess clinical usefulness of CoaguChek S and XS monitors to measure International Normalised Ratio (INR) when starting warfarin in community patients.

Methods: INR in consecutive patients starting warfarin plus enoxaparin was measured in the laboratory and on capillary blood at home using CoaguChek S or XS point of care (POC) devices. INR was measured daily until >2.0 for 2 consecutive readings. Linear regression and Bland Altman plots were derived to compare POC with laboratory INR. Percentages of POC measurements within 0.5 and 0.8 units of laboratory INR <2.0, 2.0-3.5 and >3.5 were calculated. Clinical utility was assessed using previously reported criteria.

Results: 200 CoaguChek S and 337 CoaguChek XS results were obtained from 57 and 98 patients respectively and paired with laboratory values. Correlation was acceptable between CoaguChek S and laboratory INRs (r(2)=0.7732), and excellent between CoaguChek XS and laboratory INRs (r(2)=0.9514). Bland-Altman plots showed an increasing difference between laboratory INR above 3.0 for CoaguChek S INRs but no systematic bias with increasing CoaguChek XS INRs. 83.5% of CoaguChek S and 93.5% of CoaguChek XS INRs were within 0.5 units of laboratory INR. 90% of CoaguChek S and 99.4% of the CoaguChek XS INRs were within 0.8 units of laboratory INR. Clinical agreement occurred in 89% and 99.7% of cases by expanded criteria and 82% and 99.4% of cases by narrow criteria when using CoaguChek S and CoaguChek XS respectively.

Conclusions: The CoaguChek XS is suitable for outpatient INR monitoring when starting warfarin.
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http://dx.doi.org/10.1016/j.thromres.2008.10.006DOI Listing
April 2009

Correlation between hepatitis B genotypes, 1896 precore mutation, virus loads and liver dysfunction in an Indian population.

Indian J Gastroenterol 2008 Jul-Aug;27(4):142-7

Department of Clinical Virology, Christian Medical College, Vellore, India.

Background/objectives: Hepatitis B virus (HBV) genotypes may differ in pathogenicity. However, the interplay between different virus characteristics such as genotypes, mutants and virus loads has not been well studied . We investigated the association between HBV genotype, presence of 1896 precore mutation and HBV viral loads in patients with HBV-related liver disease.

Methods: One hundred and sixteen HBV DNA-seropositive patients attending a gastroenterology outpatient clinic and 107 HBV DNA-seropositive blood donors were recruited. The subjects were stratified as those with normal (Group I, n=164) and elevated (Group II, n=59) ALT levels. The HBV genotype and the presence of the 1896 precore mutation were determined, and plasma HBV DNA levels measured.

Results: Genotype C was more common in Group II than in Group I (10 (17%) vs. 4 (2.4%); p< 0.005). There was no relationship between the 1896 precore mutation and the HBV DNA levels. Subjects with genotype C (n=14) had higher HBV DNA levels than those with genotypes A (n=33) or D (n=158).

Conclusions: The infecting genotype, but not the presence of 1896 precore mutation, correlates with HBV load. The association of genotype C with higher virus loads and with elevated ALT may point to a greater pathogenicity of this genotype.
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February 2009

Impact of pretransplant splenectomy on patients with beta-thalassemia major undergoing a matched-related allogeneic stem cell transplantation.

Pediatr Transplant 2009 Mar 14;13(2):171-6. Epub 2008 May 14.

Department of Haematology, Christian Medical College and Hospital, Vellore, India.

Impact of pretransplant splenectomy in patients with beta-thalassemia major undergoing an allogeneic SCT has never been addressed. Twenty-seven class III patients (29 transplants) had a pretransplant splenectomy. The outcome of these 29 transplants was compared with 76 transplants in class III who did not have a splenectomy. Patients in the splenectomy group were older (11.7 +/- 5.0 vs. 8.5 +/- 3.5 yr; p = 0.003) and had a larger liver size (5.7 +/- 1.8 vs. 4.4 +/- 1.6 cm; p = 0.000). Splenectomized patients had a significantly faster time to ANC >500/mm(3) (15.4 +/- 5.9 vs. 17.5 +/- 4 days; p = 0.002) and platelet >20 000/mm(3) (22.5 +/- 6.7 vs. 32.5 +/- 13.6 days; p = 0.000). The splenectomized group had a significantly reduced requirement of blood transfusion in the first 100 days post-transplant (5.5 +/- 5.1 vs. 7.2 +/- 5.4 units; p = 0.017). There were significantly more deaths related to peri-transplant infections in the post-splenectomy group (24% vs. 5.3%; p = 0.0001). The graft rejections were comparable between the two groups (20.7% vs. 14.5%; p = 0.55). The incidence of acute and chronic GVHD, late infections, and deaths from RRT was not significantly different between the two groups. The five-yr EFS (31.0 +/- 8.6 vs. 60.8 +/- 5.98; p = 0.003) and OS (39.7 +/- 9.3 vs. 71.8 +/- 5.5; p = 0.002) was significantly worse in the splenectomized group. In conclusion, pretransplant splenectomy among patients with beta-thalassemia major was associated with faster engraftment, reduced transfusion support, a higher incidence of peri-transplant infection related deaths, and a reduced EFS and OS.
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http://dx.doi.org/10.1111/j.1399-3046.2008.00953.xDOI Listing
March 2009

A model for human leukocyte antigen-matched donor-swap transplantation in India.

Transplantation 2008 Mar;85(5):687-92

Department of Nephrology, Christian Medical College, Vellore, India.

Background: In developing countries such as India, extending donor-swap transplantation (DSTx) to human leukocyte antigen (HLA)-mismatched patient-donor pairs would increase well-matched living donor kidney transplantation rates, resulting in use of less immunosuppression and less expenses, lower infective morbidity, and better survival. A model for DSTx based on HLA matching is presented.

Methods: Consecutive HLA class 1 antigen (A, B) tests of prospective renal allograft recipients and their related donors, performed at a single center in India was analyzed retrospectively using an HLA matching program to determine the proportion of prospective recipients with poorly matched related donors who could have benefited by DSTx based on HLA matching.

Results: Over the past 17.5 years, 2,129 prospective renal allograft recipients and 2,890 donors were tested for HLA class I (A and B) antigens. Of the prospective recipients, 33% did not have well-matched donors (defined as blood group compatible and sharing > or =2 of 4 HLA class I antigens). Among such recipients, 19.2% could have found a well-matched donor-swap pair within a year at a single center. This number would increase to 38% if four major national centers were involved with a shared HLA registry.

Conclusions: Nearly 40% of prospective recipients without well-matched donors would find a donor-swap pair based on HLA matching within a year, with coordination among four national centers and a shared HLA registry, increasing the well-matched living donor renal transplant rates and improving transplant outcomes. This finding is relevant in the context of Indian government amending the Transplantation of Human Organs Act to encourage DSTx.
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http://dx.doi.org/10.1097/TP.0b013e318163827eDOI Listing
March 2008

Plasmacytoid dendritic cell count on day 28 in HLA-matched related allogeneic peripheral blood stem cell transplant predicts the incidence of acute and chronic GVHD.

Biol Blood Marrow Transplant 2008 Mar;14(3):344-50

Department of Hematology, Christian Medical College, Vellore, India.

Dendritic cells (DC) are antigen-presenting cells involved in induction and regulation of immune responses. We investigated the impact of the number of infused and day 28 dendritic cells on the development of acute and chronic GVHD (aGVHD, cGVHD). Monocytoid (MC) and plasmacytoid (PC) dendritic cells were characterized as lin(-)HLA-DR(+)CD11c(+) and lin(-)HLA-DR(+)CD123(+), respectively. Sixty-eight consecutive patients who underwent HLA matched related granuloyte-colony stimulating factor (G-CSF) mobilized allogeneic PBSCT, from February 2005 to May 2006, were included in the analysis. Twenty-three patients developed aGVHD (grade II-IV) and 21 patients had cGVHD. On a univariate analysis the day 28 total DC and the day 28 MC and PC dendritic cells as continuous variables were significantly associated with development of aGVHD and cGVHD. Using an ROC plot analysis a cutoff value for total DC = 10.7/microL, MC = 9.7/microL, and PC = 4.5/microL on day 28 gave the highest likelihood ratios for aGVHD (2.7, 2.14, and 3.29, respectively). On a multivariate analysis, a low day 28 PC (
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http://dx.doi.org/10.1016/j.bbmt.2007.12.494DOI Listing
March 2008

A new stratification strategy that identifies a subset of class III patients with an adverse prognosis among children with beta thalassemia major undergoing a matched related allogeneic stem cell transplantation.

Biol Blood Marrow Transplant 2007 Aug 22;13(8):889-94. Epub 2007 Jun 22.

Department of Haematology, Christian Medical College and Hospital, Vellore, India.

One hundred ninety patients underwent 197 HLA-matched related allogeneic stem cell transplantation for a diagnosis of beta thalassemia major at our center. The median age (+/-SD) was 7+/-4.1 years, and there were 129 (68%) males. Age and liver size as continuous variables were significantly associated with an adverse outcome. Using a receiver operator characteristics curve plot analysis, cutoff values of 7 years and 5 cm for age and liver size, respectively, were associated with the highest likelihood ratio of an adverse impact. On a multivariate analysis age>or=7 years and liver size>or=5 cm had a significant impact on event free survival (EFS) (relative risk 2.2 and 2.7, P values .014 and .000, respectively). Using these 2 variables, patients were categorized as high risk if they were >or=7 years and had a liver size>or=5 cm (n=41; all belonged to Class III). The 5-year EFS and overall survival (OS) in this high-risk group was 23.93+/-6.88 and 39.01+/-7.96, whereas in the remaining Class III patients (n=64) it was 70.3+/-6.06 and 78.3+/-5.5, respectively. This risk stratification identifies a significant subset (39%) of patients among those in Class III who have a poor outcome with a conventional myeloablative allogeneic stem cell transplantation. Patients in this high-risk group would probably benefit from novel therapeutic approaches.
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http://dx.doi.org/10.1016/j.bbmt.2007.05.004DOI Listing
August 2007
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