Serum interleukin-6 in seropositive rheumatoid arthritis and response to tocilizumab: An observational study.

OBJECTIVE: There is no clinically useful biomarker as a predictor of response to any class of biological disease-modifying antirheumatic drugs (bDMARD). Serum interleukin-6 (IL-6) has a major role in the pathogenesis of rheumatoid arthritis (RA) and its serum level in patients of RA may predict response to treatment with IL-6 receptor (IL-6R) antagonist tocilizumab. METHODS: Biological DMARD naïve patients of seropositive RA, fulfilling American College of Rheumatology/European League Against Rheumatism classification criteria 2010, were treated with 06 doses of tocilizumab (8mg/kg) at monthly interval. Baseline and post-treatment serum IL-6 levels were measured and correlated with response to treatment measured by disease activity score-28 joints erythrocyte sedimentation rate (DAS28 ESR) after treatment. RESULTS: The study included 34 patients and 26 (70%) of them achieved DAS-28 remission (DAS28 ESR < 2.6). The baseline serum IL-6 did not correlate with post-treatment DAS28 ESR (R -0.197, P = .264). Though, statistically not significant (P = .085) more patients with comparatively lower baseline serum IL-6 attained DAS28 remission (16 out of 17, P = .085). There was an increase in the serum IL-6 level (median 40.5pg/ml [IQR 130.2] to 72.6pg/ml [IQR 162.5]) after tocilizumab treatment and the change in IL-6 level also did not correlate with post-treatment DAS28 ESR (R -0.240, P = .172). CONCLUSION: Higher number of patients with comparatively lower serum IL-6 level attained DAS28 remission in this study; however, it was not statistically significant. It requires further evaluation in larger studies to make any conclusion on the role of serum IL-6 as a predictor of response to tocilizumab in seropositive RA.

Assessment of ideal serum dilution for screening of antinuclear antibodies by an indirect immunofluorescence method in diagnosis of autoimmune disorders.

BACKGROUND: Time and cost constraints lead to majority of clinical laboratories deviating away from an ideal practice of checking for antinuclear antibodies (ANAs) by indirect immunofluorescence (IIF) at multiple dilutions. Usage of screening dilution of 1:40 recommended by most manufacturers of commercial ANA kits results in numerous false positive-tests and misdiagnosis of connective tissue disorders (CTDs). We sought to study the ideal screening dilution for ANA by IIF for a diagnosis of ANA-related CTDs. METHODS: Serum samples of patients with ANA-related conditions (n = 233) and healthy controls (n = 154) were evaluated by IIF using Immuno Concepts Hep-2000 ® ANA kits at dilutions from 1:40 to 1:640. Accuracy for diagnosis of CTDs for each serum dilution was assessed by receiver operating curve (ROC) analysis. RESULTS: Antinuclear antibodies (ANA) positivity was observed in 19.5%, 10.4%, 4.55%, 0.65%, and 0% of healthy controls at dilutions of 1:40, 1:80, 1:160, 1:320, and 1:640, respectively. ANA positivity at 1:40 dilution was observed among 26.4% cases with mimics of CTDs. Prevalence of ANA positivity in ANA-related CTDs was 97.3%, 96.4%, 89.3%, 83.9%, and 71.4% at dilutions of 1:40, 1:80, 1:160, 1:320, and 1:640, respectively. ROC analysis revealed best test performance for distinction between healthy and ANA-related CTD populations at a serum dilution of 1 in 80. CONCLUSIONS: Antinuclear antibodies (ANA) positivity at low titers (1:40) is highly prevalent in healthy population (19.5%) as well as amongst mimics of CTD (26.4%). Our study suggests a higher screening dilution of 1:80 for ANA by IIF for diagnosis of CTD maybe better. Combination of 1:80 and 1:160 dilutions provides optimum sensitivity and specificity for diagnosis of ANA-related disorders.

Immune activation markers in individuals with HIV-1 disease and their correlation with HIV-1 RNA levels in individuals on antiretroviral therapy.

BACKGROUND: Currently CD4+ T lymphocyte counts and HIV-1 RNA levels are being utilized to predict outcome of human immunodeficiency virus (HIV) disease. Recently, the role of immune activation in HIV disease progression and response to treatment is being investigated. This study focused on the expression of CD38 and HLA-DR on lymphocyte subsets in various groups of HIV-infected individuals and to determine their association with HIV-1 disease progression. METHODS: Ninety-eight cases of patients with HIV/AIDS in different disease stages and twenty-four healthy HIV-negative individuals were included in the cross-sectional study. Their immune function and abnormal immune activation markers (CD38 & HLA-DR) were detected using a flowcytometer, and HIV-1 RNA levels in individuals receiving antiretroviral drugs were estimated. RESULTS: The immune activation marker levels were significantly different between patients with different disease stages (P < 0.001). A significant negative correlation was observed between peripheral blood CD4+ T cell counts and immune activation markers. Also, a significant positive correlation was observed between HIV-1 RNA levels and CD38+CD8+ T lymphocyte. CONCLUSION: Immune activation markers (CD38 & HLA-DR) increase with disease progression. CD38+ on CD8+ T lymphocyte correlates well with HIV1 RNA levels in individuals failing on antiretroviral therapy.

Prevalence of occult hepatitis B amongst Indian human immunodeficiency virus type 1 infected individuals-a pilot study.

BACKGROUND: The diagnosis of hepatitis B is routinely based on the detection of hepatitis B surface antigen (HBsAg) only. However, occult hepatitis B virus (HBV) infection (OBI), which is defined as infection with positive hepatitis B core antibody (anti-HBc) antibodies, positive DNA (deoxyribonucleic acid) PCR (polymerase chain reaction), and undetectable HBsAg, as well as anti-HBs antibodies in serum or plasma of HBV infected individuals, will remain undetected using this screening diagnostic approach of detecting HBsAg. The current study aims in studying the prevalence of the OBI amongst human immunodeficiency virus type 1 (HIV-1) infected individuals who have not been exposed to anti-retroviral therapy. METHOD: Estimation of HBsAg, anti-HBs, and anti-HBc total antibody status amongst 100 HIV-1 infected study participants was carried out using enzyme-linked immunosorbent assay (ELISA) kits. Detection of HBV-DNA was carried out by in-house qualitative PCR. CD4 + T lymphocyte counts were analysed using Becton Dickinson's (BD) FACSCount™ system. RESULTS: The median age of the HIV-1 infected study population was 35 years (range: 22-67), with the gender distribution being 53 males and 47 females. The mean CD4 T lymphocyte count of the study participants was 210/mm(3). Overall, serological evidence of HBV infection was observed in 28% of the HIV-1 infected study participants. There was 5% seropositivity for HBsAg, of which 2% were additionally positive for HBV-DNA-PCR. "Anti-HBc alone" status was seen in 18% of study participants, this being statistically higher in those with CD4 T lymphocyte counts < 200/mm(3). While there was a single specimen with co-positivity for anti-HBc total antibodies and HBV-DNA, 5% of the in the study population exhibited anti-HBs antibodies positivity, with one sample exhibiting dual positivity for HBsAg and anti-HBs antibodies. CONCLUSION: Occult HBV infections may contribute to chronic liver damage, and associ-ated reactivation amongst immunocompromised individuals, HIV-1 in-fected being a subset of them. "Anti-HBc" testing followed by HBV-DNA detection by PCR can be utilised for such populations to detect OBIs. Early detection of hepatitis B viraemia will be important for deciding the antiviral therapeutic protocol so as to avoid evolution of antiviral resistance in the circulating HBV strains in HIV-1 infected individuals harbouring OBIs.

Hypertension and catecholamine levels in sleep apnoea.

BACKGROUND: Sleep-disordered breathing has been strongly associated with systemic hypertension. Increased sympathetic activity in sleep-disordered breathing may be responsible for this association. METHOD: In this sleep clinic-based study, 82 newly diagnosed patients of sleep-disordered breathing were evaluated for hypertension, and their plasma and urinary levels of catecholamines were measured. Catecholamine levels were then compared separately with the severity of sleep apnoea and blood pressure (BP). RESULTS: The prevalence of hypertension in the study population was 46.3%. The BP showed a strong and statistically significant correlation with apnoea-hypopnoea index (diastolic, r = 0.65, P < 0.001 and systolic, r = 0.60, P < 0.001) which was maintained even after the results were analysed separately for obese and non-obese subjects. Both plasma and urinary levels of catecholamines were greater in patients with severe sleep apnoea (compared to nonsevere cases) and in those with hypertension compared to normotensives. However, statistical significance was achieved only for urine catecholamines and not for plasma catechol-amines in both the cases. CONCLUSION: Hypertension is highly prevalent among Indian subjects with obstructive sleep apnoea. Catecholamine levels are significantly higher in hypertensive than in normotensive apnoeics and are also directly related to the severity of obstructive sleep apnoea. Twenty-four hour urinary catecholamine levels are more valid measures of sympathetic activity than spot plasma samples.

Correlation of CD4+ T cell Count with Total Lymphocyte Count, Haemoglobin and Erythrocyte Sedimentation Rate Levels in Human Immunodeficiency Virus Type-1 Disease.

BACKGROUND: Studies in human immunodeficiency virus (HIV) infected adults have demonstrated association of total lymphocyte count (TLC) <1200/mm (3) and subsequent disease progression or mortality. The association of other surrogate makers such as haemoglobin (Hb), and erythrocyte sedimentation rate (ESR) with CD4 count and disease progression has also been suggested. This study was carried out to determine the relationship of CD4-positive T lymphocyte counts with TLC, Hb and ESR in HIV-infected individuals. METHODS: The study population comprised of 215 antiretroviral treatment naïve HIV-1 infected adults. The CD4 positive T cell counts, TLC, Hb and ESR of study participants were measured. Spearman's rank order correlation and Receiver Operating Characteristic were used for statistical analyses. RESULT: The sensitivity, specificity, positive and negative likelihood ratios for cut-off value of TLC <1200/mm (3) for predicting CD4 counts <200 cells/mm (3) and <350 cells/mm (3) were 9.4 %, 100 %, not measurable and 1.1, and 6.1 %, 98.8 %, 5.13 and 0.95, respectively. The association of Hb (<10,11,12 g/dl and <10,12,14 g/dl for CD4 counts <200 cells/mm (3) and <350 cells/mm (3) , respectively), and ESR (<10, 20 and 30 mm fall after 1 hour) with these two CD4 counts cut-off values were suboptimal. CONCLUSION: This study reveals the poor association of TLC, Hb, and ESR with CD4 counts in HIV infected adults, thus highlighting the need to review the utility of these surrogate markers, for predicting CD4 counts in people living with HIV/AIDS.

Correlation between Systemic Lupus Erythematosus Disease Activity Index, C3, C4 and Anti-dsDNA Antibodies.

BACKGROUND: Therapeutic decisions in systemic lupus erythematosus (SLE) are based on the disease activity and nature of organ involvement. There are various clinical and laboratory methods to assess the lupus flares. METHODS: Fifty one SLE patients with active disease (lupus flare) were studied. Systemic lupus erythematosus disease activity index (SLEDAI), C3, C4 and anti-double stranded DNA levels were estimated and repeated monthly till remission. After remission these tests were done three monthly. Values of serological parameters were then correlated with SLEDAI score. RESULT: Thirteen (25.4%) patients had predominantly renal involvement while 38 (74.6%) patients had non-renal affliction. Musculoskeletal and mucocutaneous symptoms were the commonest features of lupus flare (90%). It was observed that 12 out of 13 (92.3%) patients with active renal involvement had low C3 levels and 11 (84.6%) had low C4 levels. The anti-dsDNA levels were elevated in all patients with predominant renal flare. In non-renal flare anti-dsDNA titre was raised only in 35% cases. Low C3 and C4 levels were noticed in 43% and 53% of non-renal flares respectively. Significant positive correlation was noticed between SLEDAI score and anti-dsDNA levels (0.01 level two-tailed prediction) and a significant negative correlation was observed with SLEDAI and C3, C4 levels (0.01 and 0.05 levels, two-tailed prediction) in our patients. On subgroup analysis it was noticed that this correlation is stronger for renal lupus. Negative correlation of SLEDAI and complement levels was not observed in non-renal flares. CONCLUSION: Calculation of SLEDAI is a vital clinical tool for assessment of SLE patients. Serial estimation of anti-dsDNA titre, C3 and C4 levels help us diagnose lupus flare and make appropriate therapeutic decisions in patients with high SLEDAI score.

Partner Counselling and Referral Services (PCRS) for HIV in Armed Forces - Visiting a Blind Spot.

The Indian armed forces have over 5000 cases of human immunodeficiency virus (HIV) infection since 1990. The spouses of the affected soldiers are at a constant risk of contracting infection if not informed of their husband's HIV status. The onus of counselling the spouse has been delegated to the commanding officer (CO) of the soldier as per policy. The spouses usually reside at their hometown away from the soldier's unit and bridging this "geographical discordance" and offering effective counselling becomes a tricky issue for the commanding officer (CO). This article examines the effectiveness of this strategy as practised in Indian armed forces.

A follow-up study of juvenile rheumatoid arthritis into adulthood.

AIM OF THE STUDY: To study the clinical profile of various subtypes of juvenile rheumatoid arthritis (JRA) in adulthood and analyse the outcome of the disease in terms of functional status, educational achievement, growth abnormalities, radiological progression and activity of the disease. METHODS: From a group of 150 JRA cases, 26 adult patients were included in the study. All of them were under follow up since the onset of disease in childhood. Clinical data at the onset were obtained from old medical documents. Detailed clinical and laboratory assessment of all cases were done. RESULTS: There were 10 oligoarticular, 13 polyarticular and three systemic onset cases. Mean age of onset of disease was 11.7 +/- 3.39 years (range 2-15). Mean duration of follow up was 11.4 +/- 4.46 years range (6-22). Twenty-one patients had active disease. Ninety percent of oligoarthritis group were in class 1 status whereas none of the systemic onset JRA cases were in class I. Micrognathia, short stiff neck and short stature were noticed among polyarticular and systemic onset JRA. Seventy percent of oligoarthritis group developed inflammatory low back ache. Bony ankylosis of tarsal and carpal bones were seen in eight cases. CONCLUSION: In our study there is a male predominance in JRA. Pauciarticular (oligoarthritis) JRA occurring in older boys had the best functional outcome. Growth abnormalities and radiological changes were more common in polyarticular and systemic onset JRA.

Clinical spectrum of inflammatory myositis in South India--a ten year study.

OBJECTIVE: To describe the clinical spectrum of inflammatory myopathies at a referral hospital in South India. METHODS: Patients were assessed for the pattern of muscle involvement, for the presence of arthritis, Raynaud's phenomenon, interstitial lung disease (ILD) and cardiac involvement. Muscle enzymes, electromyogram (EMG) and muscle biopsies were done. RESULTS: Eighty seven patients with inflammatory myopathies were encountered over 10 years. These included 24 with adult polymyositis, 26 with adult dermatomyositis, one with amyopathic dermatomyositis, five with juvenile myositis, one with dermatomysitis following carcinoma breast and 30 with overlap with other connective tissue diseases. There was a female preponderance (M:F = 1:2.35) except in juvenile myosits group (M:F = 1.5:1). The mean age of onset in years was 33.26 in adult polymyositis, 35.03 in adult dermatomyositis, 7.4 in juvenile dermatomyositis, 42 in malignancy-associated dermatomyositis and 25.51 in the overlap group. Proximal muscle weakness was seen in 98.8% patients, dysphagia in 33.3%, distal muscle weakness in 12.5%, respiratory muscle weakness in 9.2% and dysphonia in 4.6%. Other features included arthritis 35.63%, interstitial lung disease (ILD) 9.2%, Raynaud's 5.7%, myocarditis 4.6% and conduction disturbances 1.15%. Eleveated muscle enzymes were seen in 85.1% patients. Eletromyogram was positive in 66.6%. Muscle biopsy was positive in 85.29%. Anti-nuclear antibody was positive in 67.24%. All received steroids, non-responders needed methotrexate (13 patients) or azathioprine (11 patients). Death occurred in 10 (seven with dermatomyositis predominantly due to respiratory involvement and three with overlap). CONCLUSION: There was female preponderance except in juvenile myositis group. Proximal muscle weakness was the commonest feature. ILD was the commonest respiratory problem, while myocarditis was the commonest cardiac problem seen. Response to therapy and prognosis in polymyositis were good with no mortality during the study period. Death in the dermatomyositis group was mainly due to respiratory involvement.