Biomedical subjects

S Nityanand

Publications and source records attributed to S Nityanand.

At least 19 recordsLinked to original sources

PubMed2004

Cytokine mRNA repertoire of peripheral blood mononuclear cells in Takayasu's arteritis.

We have investigated constitutive and phytohaemagglutinin (PHA) + phorbol 12-myristate 13-acetate (PMA)-induced gene expression of tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-2, IL-3, IL-4, IL-10, IL-12 and granulocyte macrophage colony-stimulating factor (GM-CSF) in peripheral blood mononuclear cells (PBMCs) of 10 patients with Takayasu's arteritis (TA) and 10 healthy controls by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR). The constitutive mRNA expression of TNF-alpha (69.0 +/- 4.0%versus 27.5 +/- 18.0%; P = 0.001) and IL-4 (60.0 +/- 10.0%versus 0%; P = 0.001) was significantly higher in patients than controls; that of IL-3 was comparable in both groups (38.0 +/- 6.0%versus 32.0 +/- 5.0%; P = 0.651) while no constitutive mRNA expression was observed for the other cytokines studied. The stimulated PBMCs of patients, as compared with the controls, had higher mRNA gene expression of TNF-alpha (127.0 +/- 16.0%versus 54.0 +/- 6.0%; P = 0.001), IFN-gamma (93.0 +/- 13.0%versus 57.0 +/- 5.0%; P = 0.032), IL-2 (109.0 +/- 13.0%versus 68.0 +/- 6.0%; P = 0.015), IL-3 (60.0 +/- 8.0%versus 21.2 +/- 3.0%; P = 0.045) and IL-4 (68.0 +/- 7.0%versus 27.0 +/- 7.2%; P = 0.01) The mRNA expression of IL-10 was lower in patients than controls (35.0 +/- 8.0%versus 75.0 +/- 12.0%; P = 0.022). The GM-CSF mRNA was similar (102.0 +/- 6.0%versus 89.0 +/- 5.0%; P = 0.475) in both groups. Stimulation of cells with PHA + PMA showed no IL-12 expression but stimulation with lipopolysaccharide induced higher IL-12 mRNA in patients than controls (83.0 +/- 14.0%versus 33.0 +/- 4.0%; P = 0.005). Our data suggest that an inflammatory cytokine signature exists in TA with a key role for TNF-alpha, IL-4, IL-10 and IL-12 in different pathological processes of the disease.

Adolescent↗

PubMed2004

Cellular and humoral immune responses to mycobacterial heat shock protein-65 and its human homologue in Takayasu's arteritis.

Expression of heat shock protein (HSP)-65 as well as infiltration of T-cells in arterial lesions and raised levels of circulating antibodies against mycobacterial HSP65 (mHSP65) led us to the concept that mHSP65 or its human homologue (hHSP60) might be involved in the etiopathogenesis of Takayasu's arteritis (TA). Therefore, we investigated mHSP65 and hHSP60 reactive peripheral blood T-cell subsets by BrdU incorporation assay and flow cytometry as well as investigating the different isotypes of anti-mHSP65 and hHSP60 antibodies by ELISA. Eighty-four percent (22/26) of the TA patients were observed to show T-cell proliferation to mHSP65 and hHSP60 whereas only 16% (3/18) healthy controls showed such proliferation (P <0.001). Both HSPs induced proliferation of exclusively CD4+ T-cells and not CD8+ T-cells. We also observed a significantly higher prevalence of only the IgG isotype reactive to mHSP65 and hHSP60 in TA as compared to HC (mHSP65: 92% TA versus 11% HC, P <0.0001 and hHSP60: 84% versus 22%, P <0.001). Our data show a significant correlation between mHSP65 and hHSP60 reactive T-cells (CD3+: r=0.901; CD4+: r=0.968) as well as anti-mHSP65 and anti-hHSP60 IgG antibodies (r=0.814) suggesting an infection induced autoimmunity in TA, possibly induced by molecular mimicry between mHSP65 and hHSP60 or other tissue specific antigens.

Adolescent↗

PubMed2004

Interleukin-8 in Takayasu's arteritis: plasma levels and relationship with disease activity.

OBJECTIVE: To investigate the plasma levels of interleukin-8 (IL-8) in Takayasu's arteritis (TA) and their relationship with disease activity. METHODS: IL-8 levels were detected by quantitative enzyme-linked immunosorbent assay (ELISA) in the plasma of 53 TA patients, 25 age/sex-matched healthy controls and of 10 serially followed up active TA patients on immunosuppressive therapy. RESULTS: Significantly increased levels of IL-8 were observed in TA patients (26.32 +/- 48.96 pg/ml) compared to controls (6.0 +/- 2.45 pg/ml) (p = 0.0006) and in patients with active TA (55.0 +/- 71.43 pg/ml) compared to those with an inactive disease (8.94 +/- 6.35 pg/ml) (p = 0.0001). The increased levels of the chemokine were present in 37% (20/53) of the patients compared to 8% (2/25) of the controls (p < 0.01) and in 80% (16/20) of patients with active TA compared to 12% (4/33) of those with an inactive disease (p < 0.0001). In the follow-up study, the plasma levels of IL-8 were normalized in 6/10 of the patients and the disease in 5 of these 6 patients was also observed to undergo remission. CONCLUSION: These results suggest that IL-8 may play an important role in the pathogenesis of TA.

Adult↗

PubMed2003

Involvement of Fas and TNF pathways in the induction of apoptosis of T cells by antithymocyte globulin.

Antithymocyte globulin (ATG) is the treatment of choice for those aplastic anemia patients who are not suitable for bone marrow transplantation (BMT). ATG is also used for the treatment of rejections in organ transplantation and as a conditioning regimen in BMT. Despite the proven efficacy of ATG in these areas, its mechanism of action is not known. Profound T-cell lymphopenia observed in vivo with ATG treatment is supposed to contribute to its therapeutic effect. We have previously shown that apoptosis is one of the mechanisms responsible for ATG-induced lymphopenia. Our next objective was to investigate the effect of ATG on modulation of Fas and TNF pathways, the two main pathways of T-cell apoptosis. Maximum surface expression of Fas on T cells was observed after 24 h at an ATG dose of 100 microg/ml; at this dose 88% of cells expressed Fas as compared to 26% of untreated cells. Surface expression of FasL was found to peak after 24 h at an ATG dose of 1000 microg/ml when 34% of cells were positive for FasL as compared to 1.5% of untreated T cells. Tumor necrosis factor (TNF)-alpha production was found to be maximum after 6 h at 1000 microg/ml dose (20%) as measured by intracellular cytokine staining of T cells. TNF-alpha production was also measured by enzyme-linked immunosorbent assay (ELISA) in the supernatant of lymphocytes treated with ATG for 6 h. A dose-dependent increase in TNF-alpha production was found in these supernatants with a plateau being achieved at an ATG dose of 1000 micro g/ml. We conclude that ATG-induced apoptosis in T cells involves both Fas and TNF pathways and TNF-alpha is produced much earlier than Fas and FasL expression.

Antilymphocyte Serum↗

PubMed2003

Anti-annexin V antibodies in Takayasu's arteritis: prevalence and relationship with disease activity.

Annexin V has an important role in the regulation of apoptosis and antibodies directed against it have been shown to lead to apoptosis of vascular endothelial cells. To evaluate the role of anti-annexin V antibodies (AA5A) in Takayasu's arteritis (TA), we investigated these antibodies in the sera of 66 TA patients, 50 healthy controls and in the follow-up sera of 12 active TA patients by enzyme-linked immunosorbent assay. The AA5A-positive patients were analysed further for the presence of anti-endothelial cell antibodies (AECA) and anticardiolipin antibodies (ACLA) to determine the relationship of AA5A with these autoantibodies. AA5A were observed in 36% (24/66) of the patients versus 6% (3/50) of the controls (P<0.001) and in 53% (19/36) of patients with active TA versus 17% (5/30) of those with inactive disease (P<0.01). Levels of AA5A were also observed to be significantly higher in patients with TA compared to controls (0.557 +/- 0.362 versus 0.259 +/- 0.069; P<0.0001) and in patients with active disease compared to those with inactive disease (0.700 +/- 0.403 versus 0.385 +/- 0.205; P<0.0001). In the follow-up study, 6/12 patients who became inactive during follow-up also showed normalization of AA5A levels. AECA and ACLA were detected in 54% (13/24) and 12% (3/24) of the AA5A-positive patients, respectively. Our results show that a significant proportion of TA patients have AA5A, which exhibit an association with AECA and because they have a correlation with disease activity thus appear to be involved in the disease pathogenesis.

Adolescent↗

PubMed2002

Induction of apoptosis of peripheral blood mononuclear cells by antithymocyte globulin (ATG) in aplastic anemia: an in vivo and in vitro study.

Antithymocyte globulin (ATG) is the standard therapy for aplastic anemia (AA) patients who are not eligible for allogeneic bone marrow transplantation (BMT). The exact mechanism of action of ATG is still not known. Profound lymphopenia is observed throughout the treatment period with ATG and appears to contribute to its immunomodulatory effect. One of the possible mechanisms, which could account for ATG-mediated lymphopenia, is by induction of apoptosis of peripheral blood mononuclear cells (PBMCs). However, there is no conclusive evidence to support this mechanism. We investigated whether ATG could induce an in vivo apoptosis in PBMCs of 12 AA patients undergoing ATG therapy by terminal deoxynucleotidyltransferase (TdT)-mediated dUTP nick-end labeling (TUNEL) assay using flow cytometry. A significant increase in the percentage of apoptosis was observed in six patients. The median percentage prior to therapy was 3 percent (range: 1-10 percent), which increased to a peak median value of 27 percent (range 17-66 percent) with therapy. ATG also induced an in vitro apoptosis of normal PBMCs as demonstrated by Annexin V and TUNEL staining using flow cytometry. Induction of apoptosis was dose dependent: 52 percent of the PBMCs exhibited Annexin V positivity after incubation with ATG at a dose of 500 microg/ml for 6 h, and 37 percent of the PBMCs exhibited DNA fragmentation after incubation with ATG at a dose of 1000 microg/ml for 24 h as demonstrated by TUNEL assay. Thus, ATG induces in vivo apoptosis in PBMCs of AA patients undergoing therapy as well as an in vitro apoptosis in normal PBMCs, and apoptosis may be an important mechanism for ATG-induced lymphopenia.

Anemia, Aplastic↗

PubMed2001

Complement and cell mediated cytotoxicity by antiendothelial cell antibodies in Takayasu's arteritis.

OBJECTIVE: To study complement and cell mediated cytotoxicity by antiendothelial cell antibodies (AECA) in Takayasu's arteritis (TA). METHODS: Complement dependent cytotoxicity (CDC) and antibody dependent cellular cytotoxicity (ADCC) of AECA positive/negative TA sera were investigated by colorimetric MTT and 51Cr release assays, respectively, using human umbilical vein endothelial cells (HUVEC) as targets. RESULTS: Seven of 12 (58%) sera positive for IgG and/or IgM AECA exhibited CDC in comparison to none of the 13 AECA negative sera (p = 0.0052). The median value of CDC of the AECA positive group was 14% (range 13-21%) and that of the AECA negative group was 1% (p = 0.0012). Interleukin 1beta (10 U/ml) treatment of HUVEC resulted in enhancement in CDC of 6 of the 7 AECA positive cytotoxic sera, the median enhancement being 17% (range 7-29%). Tumor necrosis factor-alpha (100 U/ml) treatment of the targets resulted in a median enhancement by 36% (range 25-55%) in the CDC of 3 of these 7 sera. No sera exhibited ADCC at any of the effector:target ratios tested (10:1 to 100:1). CONCLUSION: AECA in TA mediate CDC against endothelial cells and may have a pathogenic role in the perpetuation of vascular damage in this disease.

Antibodies↗

PubMed2000

Circulating immune complexes in 50-year-old men as a strong and independent risk factor for myocardial infarction.

BACKGROUND: Circulating immune complexes (CICs) and autoantibodies against oxidatively modified LDLs (oxLDLs) and cardiolipin occur in patients with atherosclerosis and myocardial infarction (MI). The ability of such CICs and antibodies to predict myocardial infarction (MI) was investigated in a prospective nested case-control study in which healthy 50-year-old men were followed for 20 years. METHODS AND RESULTS: Two hundred fifty-seven men were included in the study, and 119 developed MI (39 died) between 50 and 70 years of age. One hundred thirty-eight randomly chosen men who did not develop MI up to 70 years of age served as controls. The prevalence of elevated levels of CICs and the concentration of CICs in men who developed MI were higher than in those who remained healthy. The concentration of CICs at age 50 was associated with a marked increased risk for MI, and this risk was independent of other conventionally recognized risk factors. There was a positive correlation between the levels of CIC and IgG antibodies to cardiolipin in men who developed MI. The level of IgG antibodies and the prevalence of elevated IgG and IgM antibodies to cardiolipin were higher in those who developed MI and had CICs than in those without CICs. Among men homozygous for C4 null alleles, those who developed MI had higher concentrations of CICs than did those who remained healthy. CONCLUSIONS: This prospective study shows that CICs alone or in combination with autoantibodies against cardiolipin in healthy males at 50 years of age predict subsequent MI between the age of and 70 years.

Aged↗

PubMed2000

Sweet's syndrome and Pneumocystis carinii pneumonia: two sequelae of low-dose cytosine arabinoside therapy in a patient with acute myeloid leukemia.

Cytosine arabinoside in low dose is sometimes employed for treating acute myeloid leukaemia. We report here a case of acute myeloid leukemia, treated with low-dose cytosine arabinoside, who developed acute febrile neutrophilic dermatosis and Pneumocystis carinii pneumonia after attainment of remission. A direct effect of cytosine arabinoside on neutrophil function and an immunosuppressive potential in lower doses could be speculated.

Adult↗

PubMed2000

Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is a rare disorder affecting predominantly children and manifesting as bone pains, bony swellings and lytic lesions. Involvement of vertebrae as presenting manifestation is unusual. Here we have presented three cases of LCH, two of multifocal eosinophilic granuloma (MEG) and one of Hand Schuller Christian disease (HSC). One of the patients with MEG; had vertebral involvement as the presenting manifestation.

Adult↗

PubMed1999

Recurrent acute coronary events in a patient with primary antiphospholipid syndrome: successful management with intracoronary stenting.

Patients with Antiphospholipid syndrome usually present with recurrent deep vein thrombosis, pulmonary thromboembolism and thromboembolic stroke. Recurrent coronary events, though reported, are rare. We describe an unusual case of Antiphospholipid syndrome who presented with recurrent acute ischaemic events in two different coronary territories, who was managed successfully with intracoronary stenting.

Adult↗

PubMed1999

C4 null alleles and myocardial infarction.

The classical risk factors, hypercholesterolemia, smoking, hypertension and diabetes, explain only a part of the epidemiological features of atherosclerotic coronary heart disease. Investigations in the past few years have shown involvement of immunological mechanisms in atherosclerosis. Circulating immune complexes accelerate atherosclerosis both in experimental animal models and in humans. The fourth component of complement (C4) plays an important role in the solubilisation and elimination of immune complexes. C4 consists of two allotypes, C4A and C4B. An earlier report showed an association between C4B null alleles (C4B*Q0) and myocardial infarction and to infarction related mortality. In the present investigation, C4A*Q0 and C4B*Q0 were studied in two population samples. The first (Group I) was a cross sectional study of 100 consecutive males with myocardial infarction before the age of 45 years and 164 population based healthy controls, age and sex matched. The second (Group II) was a nested case control study in which a cohort of 50 year-old males were followed for 20 years for development of myocardial infarction between 50-60 and 60-70 years, and the results compared with those who did not develop MI. We observed no association of homozygous and/or heterozygous C4A*Q0 or C4B*Q0 with myocardial infarction occurring in the age groups < 45, 50-60 and 60-70 years or with the infarction related mortality (P > 0.05). The prevalence/frequency of C4A*Q0 and C4B*Q0 was not related to the age at which MI occurred. The prevalence of C4A*Q0 was not affected by age. We thus conclude that partial deficiency of C4 does not appear to be a major risk factor for myocardial infarction.

Adult↗

PubMed1999

Circulating immune complexes and complement C4 null alleles in patients in patients operated on for premature atherosclerotic peripheral vascular disease.

Circulating immune complexes can lead to vascular inflammation and premature atherosclerosis and the fourth component of complement, C4, plays an important role in the removal of immune complexes. The objective of this study was to analyze the relation between circulating immune complexes and C4 null alleles in patients operated on for peripheral vascular disease before the age of 50. The prevalence of circulating immune complexes and null alleles of C4 (C4Q0) was determined in 62 patients with peripheral atherosclerosis requiring surgery before 50 years of age and in a matched control group. C4A and C4B null alleles (C4A*Q0, C4B*Q0) were determined by electrophoresis of plasma, followed by immunofixation. C4A and C4B concentrations were measured by ELISA. Circulating immune complexes were determined by sucrose density gradient centrifugation and gel filtration. There was no difference in the distribution of C4Q0 between patients and controls. The patients had higher prevalences and levels of circulating immune complexes. This was correlated with the presence of C4Q0, especially C4A*Q0. There was an inverse correlation of concentration of circulating immune complexes with C4A levels and with ratio of C4A/B levels. Thus, a significant proportion of patients with premature peripheral atherosclerosis had circulating immune complexes and C4A*Q0 enhanced the propensity to immune complex formation. This might represent one mechanism for vascular damage in this patient group.

Adult↗

PubMed1999

Anti-cardiolipin antibodies and circulating immune complexes in type 1 diabetes mellitus: increased prevalence and relation to vascular complications.

Anti-cardiolipin antibodies, oxidatively modified low-density lipoproteins (oxLDL) and circulating immune complexes are humoral factors that have been linked to vascular damage. To analyse their possible role in the vascular complications in type 1 diabetes mellitus, we investigated patients with and without vascular complications (retinopathy, nephropathy, polyneuropathy, foot ulcers). The patients were matched for age, sex and duration of diabetes. The patients were also compared with 102 healthy individuals. Anti-cardiolipin antibodies of IgG and IgA type were more common in patients compared with healthy individuals. There was no difference between patients with and without vascular complications. There was no increased prevalence of IgM anti-cardiolipin antibodies, but the levels of these antibodies were higher in patients with vascular complications compared with patients without complications and controls. Eighty-three percent of patients had circulating immune complexes in comparison with 5% of healthy individuals. Such complexes were more common in patients with complications. Both the prevalence and the levels of immune complexes were higher in patients with null alleles of complement factor C4. Patients with vascular complications had higher prevalence of C4A than of C4B null alleles. Anti-cardiolipin antibodies were present in higher relative concentrations in immune complex form than in serum in all six patients analysed. There was no increased prevalence of antibodies against oxidatively modified LDL in the patients. The higher prevalence and levels of anti-cardiolipin antibodies and circulating immune complexes in patients with vascular complications suggests that these humoral factors might be involved in the vascular complications of type 1 diabetes mellitus.

Adult↗

PubMed1998

T-cell expansions with conserved T-cell receptor beta chain motifs in the peripheral blood of HLA-DRB1*0401 positive patients with necrotizing vasculitis.

T lymphocytes are implicated in the pathogenesis of systemic vasculitis such as Wegener's granulomatosis (WG) and polyarteritis nodosa (PAN). In the present study, we have characterized in detail the T-cell receptor (TCR) of peripheral blood T cells from eight vasculitis patients of known HLA class II genotypes. We used flow cytometry to outline the exact TCR V gene expression, complementarity determining region 3 (CDR3) fragment analysis to estimate the degree of clonality and cDNA sequencing to define the exact TCR or beta chain sequences. The TCR CDR3 region interacts with antigenic peptides presented by HLA molecules, and it is normally immensely diverse. It was therefore of particular interest to identify a common dominating TCR BV8-F/L-G-G-A/Q-G-J2S3 beta chain sequence in the CD4(+) T cells of four unrelated vasculitis patients. Furthermore, this BV8-associated CDR3 motif was linked to the HLA-DRB1*0401 allele, as well as to active disease and/or an established BV8(+) CD4(+) T-cell expansion. In contrast, age- and HLA-matched patients with rheumatoid arthritis did not harbor the described BV8 motif. These results strongly suggest that BV8(+) CD4(+) T cells with the described CDR3 motif recognize a specific antigen presented by DR4 molecules, indicating the existence of a common vasculitis-associated antigen.

Adult↗

PubMed1998

Expanded T cell populations in patients with Wegener's granulomatosis: characteristics and correlates with disease activity.

Patients with Wegener's granulomatosis have a high prevalence of expanded populations of CD4+ and CD8+ T cells bearing different alpha/beta T cell receptors. To elucidate the role of these populations, we studied the phenotypic and functional characteristics of 13 expanded T cell populations in four patients for a period of 35-51 months. The expanded populations generally showed a persistently high expression of the activation markers HLA-DR and CD25. This expression was independent of the activity of the disease. The expanded populations also expressed CD45RO and/or CD45RA and most of them expressed CD57 but not CD28. Analysis of intracellular presence and secretion of IFN-gamma, IL-2, and IL-4 showed that most of the expanded cell populations contained and/or secreted more of these cytokines than the nonexpanded populations, with an especially high expression/secretion of IFN-gamma and IL-2. The expanded populations showed little proliferative response to Con A and OKT3. The proliferative response of the cells was partly restored after preincubation in medium alone. Some of the expanded populations were associated with disease activity, thus suggesting a link between expanded T cells and the disease. The activated status of the expanded populations and the tendency for certain populations to correlate in magnitude with disease activity suggest their involvement in the disease process. The relative stability of these cell populations indicates that the stimulus driving them is persistent, in agreement with the chronicity of the disease.

Aged↗

PubMed1998

Antiendothelial cell antibodies in scleroderma correlate with severe digital ischemia and pulmonary arterial hypertension.

OBJECTIVE: To determine the prevalence of IgG antiendothelial cell antibodies (AECA) in patients with scleroderma (systemic sclerosis, SSc) and to correlate it with clinical spectrum and autoantibody profile. METHODS: Seventy-six patients with SSc and 50 matched healthy controls were studied. Immunological variables were antinuclear antibody (ANA), rheumatoid factor (RF), and Scl-70. IgG-AECA was measured by cellular ELISA. RESULTS: The prevalence of IgG-AECA was 27.6% in patients with SSc compared to 6% in controls (p < 0.01). Forty percent of patients with diffuse disease had this antibody, versus 13.5% of those with limited cutaneous involvement (p < 0.05). Patients with AECA had significantly higher incidence of digital infarcts and gangrene (p < 0.01) and pulmonary arterial hypertension (p < 0.001) than those without. In the AECA positive group, mean IgG-AECA levels (measured by absorbance values) were significantly higher in patients with digital infarcts (0.91+/-0.31 vs 0.60+/-0.05; p < 0.01) and pulmonary arterial hypertension (1.14+/-0.37 vs 0.68+/-0.13; p < 0.001) compared to those without these features. CONCLUSION: IgG-AECA appears to be an important marker for disease severity in scleroderma.

Adolescent↗

PubMed1997

Immune complex mediated vasculitis in hepatitis B and C infections and the effect of antiviral therapy.

Case reports of seven patients with vasculitis and past or present viral hepatitis infection are presented, including studies on circulating immune complexes (CICs) and cryoglobulins by sucrose density gradient centrifugation or gel filtration, before and after antiviral therapy. Three patients had unusual vasculitic manifestations: coronary, large vessel, and muscle vasculitis, respectively. All the patients had high levels of CICs by the above methods, but only two had CICs by the C1q binding and conglutinin methods. The CICs/ cryoglobulins contained HBV and/or HCV antibodies, antigens, and genome. The concentration of hepatitis antibodies in immune complex form was severalfold higher than in the free form in serum. In one patient, the HBs antigen was present only in the CICs and in another, only hepatitis antibodies (no antigen/genome) were present in the serum or the cryoglobulins. With antiviral therapy, six patients went into long-lasting remissions. There was a temporal relationship between the regression of the vasculitic lesions and the decline in the levels of CICs/cryoglobulins.

Adult↗