Objective Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease, which is known ... more Objective Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease, which is known to be associated with HLA-DRB1 and Epstein–Barr virus (EBV) infection. In the Indian subcontinent where there is high seroendemicity of EBV, we postulated that the association of this virus in adult SLE (aSLE) and pediatric SLE (pSLE) patients would be different and differentially associate with the HLA-DRB1 susceptibility and protective genes. Methods A total of 109 aSLE, 52 pSLE, 215 adult healthy and 63 pediatric healthy controls were recruited. HLA-DRB1 genotyping by PCR-SSP, EBV load estimation by real-time PCR and antibody profiling (IgG & IgM) to EBV antigens by line blot assay were performed. Results DRB1*15 was found predominant in pSLE patients and DRB1*03 in aSLE patients. DRB1*15/X heterozygous was predominant in overall SLE patients, although disease severity, like hypocomplementemia, higher autoantibody levels and more organ involvement was observed in *15/*15 homozygous state. EBV strongly associated with pSLE patients showing higher percent of EA-D IgG ( p < 0.0001) and p22 IgG ( p = 0.035) along with higher viral load ( p = 0.001) as compared to healthy controls. In addition, the higher EBV DNA load significantly associated with anti-EA-D IgG ( p = 0.013) and DRB1*15/*15 ( p = 0.007) in pSLE patients as compared to aSLE patients. Conclusions This study therefore indicates that different HLA-DRB1 allotypes confer susceptibility to SLE in children and adults and disease may be triggered by increased EBV reactivation.
Background: Various studies have implicated that plasma causing transfusion-related acute lung in... more Background: Various studies have implicated that plasma causing transfusion-related acute lung injury is from alloimmunized females. The frequency of sensitization to human leukocyte antigen (HLA) was found to correlate with their parity score. No literature on the prevalence of anti-HLA antibodies in Indian blood donors is available to date. Hence, this pilot study was done to know the frequency of HLA alloimmunization in Indian blood donors. Materials and Methods: A total of 192 consenting voluntary blood donors from blood donation camps were enrolled in the study. Test group: Parous female donors (n = 96) and control group: Nulliparous female donors (n = 48) and male donors (n = 48). HLA alloimmunization was tested on the Luminex platform by screening assay to detect IgG antibodies to HLA Class I and II molecules of human origin. A mean fluoresence index of more than 2000 was considered as a positive reaction, considering the high sensitivity of Luminex assay. Results: Sixty-three out of 192 donors (32.8%) tested positive for anti-HLA antibodies, out of which 23 donors were in the control group (23.9%), and 40 donors were in the test group (41.7%); P = 0.002. On gender-based comparison, 9 out of 48 male donors (18.7%), as compared to 54 out of 144 female donors (37.5%), tested positive for HLA antibodies (P = 0.02). Based on an increase in parity score, the frequency of HLA alloimmunization was found to be significantly correlated (P = 0.002). A decrease in the trend of HLA alloimmunization was observed as the duration from the last pregnancy increased. A higher frequency of HLA alloimmunization was observed in female donors with a history of transfusion and bad obstetric history. Conclusion: The present study substantiates that plasma from parous female donors has a higher chance of containing anti-HLA antibodies as compared to nulliparous female and male donors.
Journal der Deutschen Dermatologischen Gesellschaft, Mar 1, 2022
Vitamin D hat sich als vielversprechende Behandlung für die kongenitale Ichthyose herausgestellt.... more Vitamin D hat sich als vielversprechende Behandlung für die kongenitale Ichthyose herausgestellt. Bisher liegen keine Vergleichsstudien vor.
AimAntineutrophil cytoplasmic antibody‐associated vasculitis (AAV) is an autoimmune disease chara... more AimAntineutrophil cytoplasmic antibody‐associated vasculitis (AAV) is an autoimmune disease characterized by necrotizing small vessel vasculitis that can affect various organs and present multiple symptoms. Susceptibility to AAV is multifactorial and most likely caused by an amalgamation of genetic and environmental factors. The aim of the present study was to explore the distribution of human leukocyte antigen (HLA)‐DRB1/DQB1, protein tyrosine phosphatase non‐receptor type 22 (PTPN22) and cytotoxic T‐Lymphocyte‐associated protein 4 (CTLA‐4) polymorphisms in North Indian AAV patients and their associations with clinical and pathological characteristics associated with the disease.MethodsA total of 150 AAV patients and 150 healthy controls were recruited. The clinical classification showed 128 as granulomatosis with polyangiitis (GPA) and 21 as microscopic polyangiitis. Only 1 case of eosinophilic granulomatosis with polyangiitis was encountered, which was excluded from analysis. HLA...
Background & objectives: Celiac disease (CD) can exist in various forms in type 1 diabetes (T... more Background & objectives: Celiac disease (CD) can exist in various forms in type 1 diabetes (T1D) patients and can remain undetected, leading to severe complications. This study was aimed to evaluate five commercially available anti-tissue transglutaminase (tTG) ELISA kits with distinct formats for the detection of CD and potential CD in T1D patients. Clinical and demographic profiles of the patients with different disease subsets were also studied. Methods: Fifty T1D patients with classical and non-classical symptoms of CD and 100 T1D patients without any symptoms of CD were included in this study. Anti-tTG autoantibody levels were estimated by five ELISA kits followed by histological examination of duodenal biopsy. HLA DQ2-DQ8 and DRB1-DQB1 typing was done, and serum levels for transforming growth factor (TGF)-β1 were also estimated. Results: Assay format detecting anti-tTG IgA antibodies against recombinant antigens along with neopeptides of gliadin was most efficient in the detection of CD in symptomatic patients, and assay format detecting IgA+IgG helped in the detection of potential CD in asymptomatic T1D patients. These findings were supported by histological examination and human leucocyte antigen analysis. Patients with potential CD were found to have markedly deranged glycaemic control parameters and also had significantly raised serum levels of TGF-β1, (P <0.05) compared to T1D patients. Interpretation & conclusions: Potential CD can be frequently seen in T1D patients. This can be attributed to the dietary patterns prevalent in the subcontinent and the genetic basis of the disease. Anti-tTG IgA+IgG antibodies can be useful in the detection of these potential CD cases in T1D patients. Early intervention with gluten-free diet can be considered in these patients for better disease management.
Recently, a new population of IL‐17‐producing CD4 T helper (Th) cells, named Th17, was identified... more Recently, a new population of IL‐17‐producing CD4 T helper (Th) cells, named Th17, was identified and shown to be involved in various inflammatory and autoimmune diseases, including psoriasis.
T association of seizures with anesthetic agents has been a long debate and controversy for decad... more T association of seizures with anesthetic agents has been a long debate and controversy for decades. There are several anesthetic agents that show seizure like activity after induction such as fentanyl, lignocaine, propofol, sevoflurane, and so forth. Among these agents, there are several reports of propofol, which is very frequently used as an anesthetic induction agent in India, and further approved for the induction and maintenance of anesthesia in more than 50 countries.1-3 There are several case reports indicating the status epileptogenic properties of various anesthetic agents during the induction and maintenance phase of anesthesia. Hence, the objective of the study was to evaluate the effect of propofol and associated seizure activity. The study was performed between April and May 2008 at the Department of Pharmacology, Postgraduate Institute of Medical Education & Research (PGIMER), Chandigarh, India. Institute Animals Ethics Committee (IAEC) permission was taken prior to the study, and the experimental protocol was designed and animal supervision was carried out according to the Committee for the Purpose of Control and Supervision on Experiments on Animals (CPCSEA) guidelines. A total of 36 male adult Wistar rats weighing 200-250 gm were housed in standard laboratory conditions at 25±2 ̊C, humidity of 60±2%, and 12 hours light/dark cycle. Animals were divided into 6 parallel designed groups containing 6 animals in each group. Groups were: 1) Pentylenetetrazole (PTZ) 60 mg/kg body weight intraperitoneal (i.p.) group, to observe seizure severity with a convulsive dose of PTZ. 2) PTZ 40 mg/kg i.p. group:seizure severity was assessed with a sub-maximal dose of PTZ. 3) Propofol low dose group (2 mg/kg i.p.): in this group the rats were treated with propofol and observed for seizure onset and severity. 4) Propofol high dose group (5 mg/kg i.p.), similar to the 2mg/kg i.p. group, only the dose was increased. 5) Combination of propofol low dose (2 mg/kg i.p.) + PTZ 40 mg/kg i.p. group: rats were treated with propofol and PTZ to check the seizure onset. Twenty-four hours following propofol administration, seizure susceptibility was carried out. 6) Combination of propofol high dose (5 mg/kg i.p.) + PTZ 40 mg/kg i.p., similar to the previous combination group. Thereafter seizure susceptibility was assessed by administration of PTZ at the dose of 60 mg/kg i.p. and 40 mg/kg i.p. after 24 hours of propofol treatment. Seizures were recorded on a 7 point seizure score according to the following scale: 0 no response; 1 ear and facial twitching; 2 one to 20 myoclonic body jerks in 10 minutes; 3 more than 20 body jerks in 10 minutes; 4 clonic forelimb convulsions; 5 generalized clonic convulsions with rearing and falling down episodes, and 6 generalized convulsions with tonic extension episodes.4 The induction of apoptosis was detected by the DNA fragmentation method. This method employs the agarose gel electrophoresis, which measures DNA fragmentation in nuclear extracts showing the typical “DNA-ladder” configuration. The rats were sacrificed by cervical dislocation under deep anesthesia. The brain was dissected out and immediately transfer to ice chilled normal saline. Thereafter, DNA fragmentation was carried out by phenol-chloroform extraction method and assessed by the agarose gel electrophoresis. The data were entered into the Statistical Package for Social Sciences (SPSS Inc, Chicago, IL, USA) version 12.0 and appropriate nonparametric Kruskal-Wallis test were applied. P-value of <0.05 was considered statistically significant. The seizure severity was measured using a 0-6 score as per their severity following a subconvulsive dose of PTZ. The seizure severity score was found significantly increased in the (PTZ+Pro 5) group as compared with other treatment groups (p<0.05). However, propofol at 2 mg/kg + PTZ (PTZ+Pro 2) showed a marginal increase in seizure severity. The DNA fragmentation of these groups was carried out 24 hours after propofol treatment. The DNA fragmentation was observed in a concentration-dependent manner in propofol 2 mg/kg + PTZ 40 mg/kg (PTZ 40 + Pro 2) and propofol 5 mg/ kg + PTZ 40 mg/kg (PTZ 40 + Pro 5) groups (Figure 1). Hence, the findings of present study suggested that a sub-convulsive dose of PTZ potentiates the DNA fragmentation of propofol. A study by Tsuchiya et al,5 showed that propofol induced apoptosis through cell surface death receptor activation and activation of the mitochondrial pathway with cytosolic release of cytochrome c. Hence, it was hypothesized that apoptosis by propofol is induced by the cell surface death receptor pathway and the mitochondrial pathway. However, the present study concluded no significant difference in DNA fragmentation in the lower dose (2 mg/kg) as well as with the higher dose of propofol (5 mg/kg) except in the combination group Brief Communication
Objective Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease, which is known ... more Objective Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease, which is known to be associated with HLA-DRB1 and Epstein–Barr virus (EBV) infection. In the Indian subcontinent where there is high seroendemicity of EBV, we postulated that the association of this virus in adult SLE (aSLE) and pediatric SLE (pSLE) patients would be different and differentially associate with the HLA-DRB1 susceptibility and protective genes. Methods A total of 109 aSLE, 52 pSLE, 215 adult healthy and 63 pediatric healthy controls were recruited. HLA-DRB1 genotyping by PCR-SSP, EBV load estimation by real-time PCR and antibody profiling (IgG &amp; IgM) to EBV antigens by line blot assay were performed. Results DRB1*15 was found predominant in pSLE patients and DRB1*03 in aSLE patients. DRB1*15/X heterozygous was predominant in overall SLE patients, although disease severity, like hypocomplementemia, higher autoantibody levels and more organ involvement was observed in *15/*15 homozygous state. EBV strongly associated with pSLE patients showing higher percent of EA-D IgG ( p &lt; 0.0001) and p22 IgG ( p = 0.035) along with higher viral load ( p = 0.001) as compared to healthy controls. In addition, the higher EBV DNA load significantly associated with anti-EA-D IgG ( p = 0.013) and DRB1*15/*15 ( p = 0.007) in pSLE patients as compared to aSLE patients. Conclusions This study therefore indicates that different HLA-DRB1 allotypes confer susceptibility to SLE in children and adults and disease may be triggered by increased EBV reactivation.
Background: Various studies have implicated that plasma causing transfusion-related acute lung in... more Background: Various studies have implicated that plasma causing transfusion-related acute lung injury is from alloimmunized females. The frequency of sensitization to human leukocyte antigen (HLA) was found to correlate with their parity score. No literature on the prevalence of anti-HLA antibodies in Indian blood donors is available to date. Hence, this pilot study was done to know the frequency of HLA alloimmunization in Indian blood donors. Materials and Methods: A total of 192 consenting voluntary blood donors from blood donation camps were enrolled in the study. Test group: Parous female donors (n = 96) and control group: Nulliparous female donors (n = 48) and male donors (n = 48). HLA alloimmunization was tested on the Luminex platform by screening assay to detect IgG antibodies to HLA Class I and II molecules of human origin. A mean fluoresence index of more than 2000 was considered as a positive reaction, considering the high sensitivity of Luminex assay. Results: Sixty-three out of 192 donors (32.8%) tested positive for anti-HLA antibodies, out of which 23 donors were in the control group (23.9%), and 40 donors were in the test group (41.7%); P = 0.002. On gender-based comparison, 9 out of 48 male donors (18.7%), as compared to 54 out of 144 female donors (37.5%), tested positive for HLA antibodies (P = 0.02). Based on an increase in parity score, the frequency of HLA alloimmunization was found to be significantly correlated (P = 0.002). A decrease in the trend of HLA alloimmunization was observed as the duration from the last pregnancy increased. A higher frequency of HLA alloimmunization was observed in female donors with a history of transfusion and bad obstetric history. Conclusion: The present study substantiates that plasma from parous female donors has a higher chance of containing anti-HLA antibodies as compared to nulliparous female and male donors.
Journal der Deutschen Dermatologischen Gesellschaft, Mar 1, 2022
Vitamin D hat sich als vielversprechende Behandlung für die kongenitale Ichthyose herausgestellt.... more Vitamin D hat sich als vielversprechende Behandlung für die kongenitale Ichthyose herausgestellt. Bisher liegen keine Vergleichsstudien vor.
AimAntineutrophil cytoplasmic antibody‐associated vasculitis (AAV) is an autoimmune disease chara... more AimAntineutrophil cytoplasmic antibody‐associated vasculitis (AAV) is an autoimmune disease characterized by necrotizing small vessel vasculitis that can affect various organs and present multiple symptoms. Susceptibility to AAV is multifactorial and most likely caused by an amalgamation of genetic and environmental factors. The aim of the present study was to explore the distribution of human leukocyte antigen (HLA)‐DRB1/DQB1, protein tyrosine phosphatase non‐receptor type 22 (PTPN22) and cytotoxic T‐Lymphocyte‐associated protein 4 (CTLA‐4) polymorphisms in North Indian AAV patients and their associations with clinical and pathological characteristics associated with the disease.MethodsA total of 150 AAV patients and 150 healthy controls were recruited. The clinical classification showed 128 as granulomatosis with polyangiitis (GPA) and 21 as microscopic polyangiitis. Only 1 case of eosinophilic granulomatosis with polyangiitis was encountered, which was excluded from analysis. HLA...
Background & objectives: Celiac disease (CD) can exist in various forms in type 1 diabetes (T... more Background & objectives: Celiac disease (CD) can exist in various forms in type 1 diabetes (T1D) patients and can remain undetected, leading to severe complications. This study was aimed to evaluate five commercially available anti-tissue transglutaminase (tTG) ELISA kits with distinct formats for the detection of CD and potential CD in T1D patients. Clinical and demographic profiles of the patients with different disease subsets were also studied. Methods: Fifty T1D patients with classical and non-classical symptoms of CD and 100 T1D patients without any symptoms of CD were included in this study. Anti-tTG autoantibody levels were estimated by five ELISA kits followed by histological examination of duodenal biopsy. HLA DQ2-DQ8 and DRB1-DQB1 typing was done, and serum levels for transforming growth factor (TGF)-β1 were also estimated. Results: Assay format detecting anti-tTG IgA antibodies against recombinant antigens along with neopeptides of gliadin was most efficient in the detection of CD in symptomatic patients, and assay format detecting IgA+IgG helped in the detection of potential CD in asymptomatic T1D patients. These findings were supported by histological examination and human leucocyte antigen analysis. Patients with potential CD were found to have markedly deranged glycaemic control parameters and also had significantly raised serum levels of TGF-β1, (P <0.05) compared to T1D patients. Interpretation & conclusions: Potential CD can be frequently seen in T1D patients. This can be attributed to the dietary patterns prevalent in the subcontinent and the genetic basis of the disease. Anti-tTG IgA+IgG antibodies can be useful in the detection of these potential CD cases in T1D patients. Early intervention with gluten-free diet can be considered in these patients for better disease management.
Recently, a new population of IL‐17‐producing CD4 T helper (Th) cells, named Th17, was identified... more Recently, a new population of IL‐17‐producing CD4 T helper (Th) cells, named Th17, was identified and shown to be involved in various inflammatory and autoimmune diseases, including psoriasis.
T association of seizures with anesthetic agents has been a long debate and controversy for decad... more T association of seizures with anesthetic agents has been a long debate and controversy for decades. There are several anesthetic agents that show seizure like activity after induction such as fentanyl, lignocaine, propofol, sevoflurane, and so forth. Among these agents, there are several reports of propofol, which is very frequently used as an anesthetic induction agent in India, and further approved for the induction and maintenance of anesthesia in more than 50 countries.1-3 There are several case reports indicating the status epileptogenic properties of various anesthetic agents during the induction and maintenance phase of anesthesia. Hence, the objective of the study was to evaluate the effect of propofol and associated seizure activity. The study was performed between April and May 2008 at the Department of Pharmacology, Postgraduate Institute of Medical Education & Research (PGIMER), Chandigarh, India. Institute Animals Ethics Committee (IAEC) permission was taken prior to the study, and the experimental protocol was designed and animal supervision was carried out according to the Committee for the Purpose of Control and Supervision on Experiments on Animals (CPCSEA) guidelines. A total of 36 male adult Wistar rats weighing 200-250 gm were housed in standard laboratory conditions at 25±2 ̊C, humidity of 60±2%, and 12 hours light/dark cycle. Animals were divided into 6 parallel designed groups containing 6 animals in each group. Groups were: 1) Pentylenetetrazole (PTZ) 60 mg/kg body weight intraperitoneal (i.p.) group, to observe seizure severity with a convulsive dose of PTZ. 2) PTZ 40 mg/kg i.p. group:seizure severity was assessed with a sub-maximal dose of PTZ. 3) Propofol low dose group (2 mg/kg i.p.): in this group the rats were treated with propofol and observed for seizure onset and severity. 4) Propofol high dose group (5 mg/kg i.p.), similar to the 2mg/kg i.p. group, only the dose was increased. 5) Combination of propofol low dose (2 mg/kg i.p.) + PTZ 40 mg/kg i.p. group: rats were treated with propofol and PTZ to check the seizure onset. Twenty-four hours following propofol administration, seizure susceptibility was carried out. 6) Combination of propofol high dose (5 mg/kg i.p.) + PTZ 40 mg/kg i.p., similar to the previous combination group. Thereafter seizure susceptibility was assessed by administration of PTZ at the dose of 60 mg/kg i.p. and 40 mg/kg i.p. after 24 hours of propofol treatment. Seizures were recorded on a 7 point seizure score according to the following scale: 0 no response; 1 ear and facial twitching; 2 one to 20 myoclonic body jerks in 10 minutes; 3 more than 20 body jerks in 10 minutes; 4 clonic forelimb convulsions; 5 generalized clonic convulsions with rearing and falling down episodes, and 6 generalized convulsions with tonic extension episodes.4 The induction of apoptosis was detected by the DNA fragmentation method. This method employs the agarose gel electrophoresis, which measures DNA fragmentation in nuclear extracts showing the typical “DNA-ladder” configuration. The rats were sacrificed by cervical dislocation under deep anesthesia. The brain was dissected out and immediately transfer to ice chilled normal saline. Thereafter, DNA fragmentation was carried out by phenol-chloroform extraction method and assessed by the agarose gel electrophoresis. The data were entered into the Statistical Package for Social Sciences (SPSS Inc, Chicago, IL, USA) version 12.0 and appropriate nonparametric Kruskal-Wallis test were applied. P-value of <0.05 was considered statistically significant. The seizure severity was measured using a 0-6 score as per their severity following a subconvulsive dose of PTZ. The seizure severity score was found significantly increased in the (PTZ+Pro 5) group as compared with other treatment groups (p<0.05). However, propofol at 2 mg/kg + PTZ (PTZ+Pro 2) showed a marginal increase in seizure severity. The DNA fragmentation of these groups was carried out 24 hours after propofol treatment. The DNA fragmentation was observed in a concentration-dependent manner in propofol 2 mg/kg + PTZ 40 mg/kg (PTZ 40 + Pro 2) and propofol 5 mg/ kg + PTZ 40 mg/kg (PTZ 40 + Pro 5) groups (Figure 1). Hence, the findings of present study suggested that a sub-convulsive dose of PTZ potentiates the DNA fragmentation of propofol. A study by Tsuchiya et al,5 showed that propofol induced apoptosis through cell surface death receptor activation and activation of the mitochondrial pathway with cytosolic release of cytochrome c. Hence, it was hypothesized that apoptosis by propofol is induced by the cell surface death receptor pathway and the mitochondrial pathway. However, the present study concluded no significant difference in DNA fragmentation in the lower dose (2 mg/kg) as well as with the higher dose of propofol (5 mg/kg) except in the combination group Brief Communication
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