Sabiha Anis

CLINICAL PROFILE AND HLA TYPING OF AUTOIMMUNE HEPATITIS FROM PAKISTAN

Background Human leukocyte antigen (HLA) typing in autoimmune hepatitis (AIH) has been investigated in different populations and ethnic groups, but no such data is available from Pakistan. Objectives The aim of this study was to evaluate the clinical profile of autoimmune hepatitis (AIH), and determine the associated antigens and alleles by performing HLA typing. Patients and Methods A total of 58 patients, diagnosed and treated as AIH in the last 10 years were reviewed. Diagnosis was based on International AIH Group criteria. Forty one patients underwent liver biopsy. HLA typing was performed in 44 patients and 912 controls by serological method for HLA A and B, and by PCR technique using sequence specific primers for DR alleles. Results Of 58 cases, 35 were females (60.3%). The median age was 14.5 (range 4-70 years), and AIH score was 14 (10-22). Thirty-six (62.0%) patients had type 1 AIH, 10 (17.2%) type 2, and the remaining 12 were seronegative with biopsy proven AIH. Forty-nine patients (84.4%) had cirrhosis. Twenty-four (41.4%) patients had ascites at the time of presentation. Among 41 patients who underwent liver biopsy, thirty-two had advance stages III and IV disease, and twenty had severe grade of inflammation. Fifteen patients had other associated autoimmune diseases and one developed hepatocellular carcinoma. HLA A2 (P = 0.036), HLA A9 (23) (P = 0.018), HLA A10 (25) (P = 0.000), HLA A19 (33) (P = 0.000), HLA B15 (63) (P = 0.007), HLA B40 (61) ( P = 0.002), HLA DR6 (P = 0.001) with its subtypes HLA-DRB1*13 (P = 0.032) and HLA-DRB1*14 (p = 0.017) were more prevalent in AIH with statistical significance than controls. Conclusions AIH in our region presents with advanced disease affecting predominantly children and adolescents. There is a genetic association of HLA DR6 along with other alleles and antigens in our patients with AIH.

Vasculitis with renal involvement in essential mixed cryoglobulinemia: Case report and mini-review

The discovery of a strong association between hepatitis C virus (HCV) infection and mixed cryoglobulinemia (MC) has led to an increasingly rare diagnosis of idiopathic essential MC (EMC). The incidence of EMC is high in regions where there is a comparatively low HCV infection burden and low in areas of high infection prevalence, including HCV. The diagnosis of EMC requires an extensive laboratory investigation to exclude all possible causes of cryoglobulin formation. In addition, although cryoglobulin testing is simple, improper testing conditions will result in false negative results. Here, we present a 46-year-old female patient with a case of EMC with dermatological and renal manifestations, highlighting the importance of extensive investigation to reach a proper diagnosis. We review the need for appropriate laboratory testing, which is often neglected in clinical practice and which can result in false negative results. This review also emphasizes the significance of an extended testing repertoire necessary for better patient management. Despite a strong association of MC with HCV infection and other causes that lead to cryoglobulin formation, EMC remains a separate entity. Correct diagnosis requires proper temperature regulation during sample handling, as well as characterization and quantification of the cryoprecipitate. Inclusion of rheumatoid factor activity and complement levels in the cryoglobulin test-panel promotes better patient management and monitoring. Consensus guidelines should be developed and implemented for cryoglobulin detection and the diagnosis of cryoglobulinemic syndrome, which will reduce variability in inter-laboratory reporting.

Clinical Significance of Anti-Ribosomal P Protein Antibodies in Patients with Lupus Nephritis

BACKGROUND Systemic Lupus Erythematosus (SLE) is a chronic inflammatory disorder affecting multiple systems of the body. Clinical features show wide variations in patients with the different ethnic background. Renal involvement is a predictor of poor prognosis. Immunological workup is an integral part of SLE diagnostic criteria. Anti-ribosomal P Protein (anti-P) antibodies are highly specific for SLE. They may be present in Antinuclear Antibodies (ANA) negative SLE patients. Their role in Lupus Nephritis (LN) is under debate, some researchers found them associated with poor prognosis whereas others found favorable effect of these antibodies on renal disease. OBJECTIVE In this study, we investigated frequency of anti-P antibodies and the effect of these antibodies on renal functions in the LN patients. METHODS A total of 133 SLE patients were enrolled in this study. All patients had ANA in their sera. Anti-P antibodies along with other autoantibodies against extractable nuclear antigens (anti-Sm, anti- SS-A, anti-SS-B, anti-histones and anti-RNP) were detected by Immunoblot assay. Anti-dsDNA antibodies were detected by indirect Immunofluorescence Assay (IFA). RESULTS We found anti-P antibodies in 10.5% LN patients. Interestingly their presence in association with anti-dsDNA was associated with improved renal functions in comparison to those who had antidsDNA antibodies in isolation (serum creatinine: 1.3 ± 0.8 mg/dl vs. 3.0 ± 3.0; P= 0.091). CONCLUSION Anti-dsDNA antibodies are directly involved in renal pathology in SLE patients. As these antibodies are nephrotoxic, concomitant occurrence of anti-P antibodies seems to offer a shielding effect on renal functions, which was evident by normal serum creatinine levels. Therefore, anti-P antibodies may be considered as a good prognostic marker in these patients.

T and B cells immunophenotypes in blood and urine of patients with focal segmental glomerulosclerosis in relation todisease severity

Background: Disordered immune system is responsible for the pathogenesis in most of the glomerulonephritis (GN) including FSGS. Elucidation of involvement of immune cells is important to avoid invasive procedures for monitoring of disease progression. Methods: We analyzed the frequencies of CD25, CD122 and CD5 on CD4+, CD8+ and CD19+ T and B cells in blood and urine samples of 50 individuals including FSGS, other GN, pathological controls (PC)) and healthy controls (HC)). Data was analyzed using spss software. Results: The ratio of CD4+25+to CD4+122+ was found significantly low in blood of FSGS patients compared to HC and PC (37.6 ± 44.1% vs. 100% in HC and PC, P = 0.000). The ratio of CD19+25+ to CD19+122+ cells were also significantly low in FSGS compared to HC (21.6 ± 20.6% vs.9.4 ± 7.7%, P =0.021) . Overall, the percentages CD4+ 25+ 122+, CD8+25+ 122+and CD19+25+ 122+ cells were more in the urine of FSGS patients compared to controls. CD19+5+ B cells were significantly high in blood and urine of FSGS compared to controls. These cells were also significantly more in the blood of steroid dependent and resistant FSGS patients compared to steroid responsive and in urine of patients with renal dysfunction compared to normal renal functions. Conclusions: Our results show that T and B cells have a definite role in the pathogenesis of FSGS. A low expression of CD25 found on T and B cells in FSGS found in this study indicate down regulation of Treg and Breg cells in these patients. A high expression of CD5+B in blood and urine of FSGS may be responsible for disease severity. The results of this study are important as it may help in avoiding unnecessary invasive procedure for patient monitoring. However there is a need to do further studies to validate these results.

Immunologists' perspective of nephropathology.

Please cite this paper as: Anis S. Immunologists’ perspective of nephropathology. J Nephropathol. 2016;5(2):62-64. DOI: 10.15171/jnp.2016.11

Platelet count to splenic diameter ratio and splenoportal index as non-invasive screening tools in predicting esophageal varices in patients with liver cirrhosis

Abstract Background: Esophageal varices (EVs) are serious consequences of liver cirrhosis. Several studies have evaluated the possible non-invasive markers for the diagnosis of EVs to reduce the number of endoscopic procedures in patients with cirrhosis but without varices. This study was performed to evaluate the diagnostic performance of two such parameters (platelet count to splenic diameter ratio and splenoportal index) for the detection of EVs. Materials and Methods: A total of 111 patients with liver cirrhosis were analyzed after performing upper gastrointestinal endoscopy and non-invasive tests including platelet count and ultrasound abdomen including Doppler study. Appropriate statistical tests were applied to compare the non-invasive tests with the gold standard of endoscopy. Results: Of 111 liver cirrhotics, 80 (72.1%) were male and 31 (27.9%) were female. EVs were present in 68 (61.3%) patients and absent in 43 (38.7%) patients. In platelet count to splenic diameter ratio, a cut-off value of 1014 was obtained, which gave a sensitivity of 75.0%, specificity of 65.1%, positive predictive value (PPV) of 77.3%, negative predictive value (NPV) of 62.2% and diagnostic accuracy of 71.2%. In the splenoportal index, a cut-off value of 3.5 cm/s was obtained, which gave a sensitivity of 79.4%, specificity of 72.0%, PPV of 81.8%, NPV of 68.8% and diagnostic accuracy of 76.5% for the diagnosis of EVs. Conclusions: The platelet count to spleen diameter ratio and splenoportal index are non-invasive and fairly accurate alternatives in identifying the presence or absence of EVs in patients with compensated cirrhosis.