anti-ENA Antibodies Research Articles

HLA-DR genotypes in patients with primary Sjögren's syndrome in Taiwan.

Different human leukocyte antigen (HLA) genotypes have been known to be associated with the risk of development of Sjögren's syndrome in different populations, but this association has never been reported in Taiwan. We enrolled 1044 subjects (673 patients, 371 controls) and tested their HLA-DR genotypes. We found an increased risk of Sjögren's syndrome in patients carrying HLA-DR8. DR1 and DR14 were associated with increased risk of eye involvement (uveitis, scleritis or optic neuritis), while DR15 was associated with increased risk of interstitial lung disease. DR8 was associated with increased risk of formation of multiple antibodies: anti-Ro, rheumatoid factor and antinuclear antibodies (ANA) reaching titer 1:80 or above. DR9 was associated with decreased risk of formation of anti-La antibodies and increased risk of formation of antithyroglobulin antibodies. DR10 was associated with risk of formation of anticyclic citrullinated peptide (anti-CCP) antibodies, and DR11 was associated with increased risk of formation of anti-La antibodies. Oral ulcer was found to be negatively associated with anti-Ro antibodies and with anti-ENA antibodies. Skin lesions were associated with ANA antibody titer elevation to 1:80 or above. Malignancies of any kind were associated with the presence of cryoglobulin. Females were more likely to be diagnosed at a younger age than males. There was no statistically significant relationship between HLA-DR genotype and age at disease diagnosis. In patients with Sjögren's syndrome in Taiwan, the presence of HLA-DR8 appeared to be a risk factor. In addition, we found several associations between HLA-DR genotype, clinical presentation, and autoantibody status among them.

Evaluation of a New Multiparametric Microdot Array-Based Immunoassay Panel for Systemic Autoimmune Disease Diagnosis.

The early reliable detection and quantification of autoantibodies play an important role in autoimmune disease diagnosis and in disease-course monitoring. New technologies, such as the multiplexed determination of autoantibodies, have recently been introduced and are being adopted more frequently. The aim of this study was to evaluate the ability of a new microdot array-based multiparametric assay (ZENIT AMiDot CTD panel, A. Menarini Diagnostics, Firenze, Italy) to correctly classify patients with autoimmune rheumatic diseases (ARDs) and compare it to a fluorescence enzyme immunoassay (FEIA) for the detection of anti-ENAs. The study included 69 consecutive samples from patients with ARDs that were analyzed using two different methods (FEIA and AMiDot) to detect anti-CENP B and six anti-ENA antibodies: anti-Scl-70, anti-SSB/La, anti-Jo-1, anti-U1-RNP, anti-Ro52, and anti-Ro60. The control group sera came from sixty-eight blood donors. Tests were run on the automated slide processor ZENIT FLOW, and then the slides were imaged and analyzed using ZENIT fast. Since the samples were selected for at least one antibody positivity with an ARD diagnosis, we did not calculate clinical sensitivity but only specificity, which was 98.53%, ranging from 90% for anti-SSB/La antibodies to 100% for anti-CENP B ones. Mean agreement among the methods assessed by Cohen's kappa was 0.816 ± 0.240. The assay demonstrated good clinical performance and may be considered a valuable aid in detecting ARD patients, offering an alternative to methods such as FEIA which are largely in use today.

Hybrid glycophorin GP (A-B) and anti-Ena antibody in a multiparous woman

Abstract The MNS system is a large, complex group of antigens, with 50 antigens at present. The major antigens of the system are carried on glycophorins A and B, which are important red cell sialoglycoproteins. Altered expression of MNS antigens is possible in cases where there is a formation of hybrid glycophorins. Some of these patients may make clinically significant antibodies which can be associated with hemolytic transfusion reactions (HTR) or hemolytic disease of the fetus and the newborn. This is a report of one such case with both these phenomena, in a multiparous woman. Incompatible cross-matches at the referral center caused the samples to be sent to this immunohematological laboratory where the serological profile was detailed. On sending the samples to a third blood group reference laboratory, gene sequencing was done and the antibody was identified. At this immunohematological laboratory, the phenotype was determined as M-N+. The patient’s sera showed panreactivity with all panel cells (3-cell and 11-cell). At blood group reference laboratory, the findings were as follows- GYP (A-B) hybrid gene consistent with hemi/homozygosity for GYP*JL was confirmed and the panreactive antibody was identified as anti - Ena. Rare, atypical phenotypes in the MNS system can result from mutations affecting the sialoglycoproteins the antigens are carried on. The subset of antigens expressed in individual phenotypes varies and these patients can develop antibodies against the antigens they lack. When they present with immunohematological challenges such as panreactivity and incompatibility, a combination of serology, molecular technologies, and family studies help solve the problem. Alternatives to transfusion are also useful options in managing such cases.

Association of urine autoantibodies with disease activity in systemic lupus erythematosus.

The presence of urinary autoantibodies in patients with systemic lupus erythematosus (SLE) has been confirmed by several studies; however, the significance of their presence in urine remains unclear. This study aims to further investigate the association between urine autoantibodies and disease activity as well as organ involvement in SLE. This cross-sectional study included 89 SLE patients. Data collected included anti-nuclear antibody (ANA), anti-ENA antibodies, and anti-dsDNA antibody levels in both serum and urine, complement (C) 3, C4 levels in serum, SLE disease activity index-2000 (SLEDAI-2000), renal domains of SLEDAI (RSLEDAI) and non-renal SLEDAI (NRSLEDAI). The rate of positive urine ANA (uANA) was 33.3% (29/87) among the enrolled patients. Compared to the uANA negative group, the positive group exhibited significantly higher SLEDAI-2000 scores (7.85 ± 5.88 vs. 18.69 ± 6.93, p < 0.001), RSLEDAI scores [0 (0, 4.0) vs. 12.0 (8.0, 16.0), p < 0.001], and NRSLEDAI [4 (2.0, 8.0) vs. 6.0 (4.0, 9.5), p = 0.038]. Patients with positive urine anti-Sm antibody demonstrated significantly elevated SLEDAI-2000 scores compared to those who were negative (25.0 ± 8.80 vs. 10.09 ± 6.63, p < 0.001). Similarly, they also had higher RSLEDAI [16.0 (12.0, 16.0) vs. 4.0 (0, 8.0), p < 0.001] and NRSLEDAI [9.5 (6.0, 13.5) vs. 4.0 (3.0, 8.0), p = 0.012], as well as a greater prevalence of renal involvement compared to their negative counterparts (100% vs. 58.2, p = 0.022). There was a positive correlation between uANA titer and both SLEDAI-2000 (rs = 0.663, p < 0.001) and RSLEDAI (rs = 0.662, p < 0.001). The serum anti-dsDNA antibody level did not exhibit a significant correlation with RSLEDAI (rs = 0.143, p = 0.182). Conversely, the urine anti-dsDNA antibody level demonstrated a significant positive correlation with RSLEDAI (rs = 0.529, p < 0.001). Urine ANA is associated with both global SLEDAI and RSLEDAI scores. Urine anti-Sm antibody is associated with an increased incidence of renal involvement in SLE. The urine anti-dsDNA antibody level, rather than the serum anti-dsDNA antibody level, exhibits a significant association with RSLEDAI in SLE.

The profile of soluble anti-antigen antibodies detected by Immundot: Experience of the Immunology laboratory, University Hospital Hassan II-Fez, Morocco.

Introduction: Soluble anti-antigen antibodies (Anti-ENA) represent a specificity of anti-nuclear autoantibodies (ANA), which are directed against nuclear particles composed of small RNA (Ribonucleic acid) and proteins. They are found during certain autoimmune diseases (ADs), most frequently during systemic lupus erythematosus (SLE) and Gougerot syndrome. The aim of this study is to retrospectively analyze the positive serum for Anti-ENA antibodies and associated pathologies. Materials and methods: This study was carried out at the Immunology Department, Central Laboratory of Medical Analysis, University Hospital Hassan II - Fez, Morocco, for a period of 2 years. 821 serum samples were included. The indirect immunofluorescence method (IFI) was used to search the ANAs in the serums. In the case of a positive result, an identification of the antigenic targets was performed by the Immunodot technique according to the supplier's recommendations (D-Tek). Results: Eighty-eight serums were found positive for anti-ENA antibodies. The mean age in our series was 41 ±15.5 years. There were 80 women and 8 men with a sex ratio F/M of 10. The results by associated pathologies show a strong association of the anti-ENA antibodies' positivity with lupus and Gougerot syndrome. Conclusion: Anti-ENA antibodies are important immunological markers for lupus and Gougerot syndrome diagnosis.

Determination of specific autoantibodies in patients with systemic lupus erythematosus by Line immunoassay, ELISA and CLIF assay.

Detection of specific antinuclear-antibodies is very importance in term of diagnosis, prognosis and management of patients with systemic lupus erythematosus (SLE). To date, Line immunoassay (LIA), enzyme-linked immunosorbent assay (ELISA) and Crithidia luciliae indirect immunofluorescence (CLIF) assay are commonly used for detection of specific antinuclear-antibodies. To determine the performance of LIA, ELISA and CLIF for the detection of anti-double-stranded DNA (dsDNA), anti-nucleosome, and anti-extractable nuclear antigens (ENA) antibodies in patients with SLE. A total 100 sera from 50 patients with SLE, 25 patients with disease control and 25 healthy control subjects were tested for anti-dsDNA, anti-nucleosome, and anti-ENA antibodies by LIA, ELISA, and CLIF assay. Agreement and diagnostic performance of each assay were analyzed using Cohen's kappa coefficient and receiver operating characteristic curve analysis. For the detection of anti-dsDNA antibody, ELISA had a substantial agreement with CLIF assay (? = 0.74) but LIA had a fair agreement with ELISA and CLIF assay (? = 0.37, and 0.35 respectively). For the detection of anti-nucleosome, anti-nRNP/Sm, anti-Sm, anti-SSA, and anti-SSB antibodies, LIA had a substantial to perfect agreement with ELISA (? = 0.64, 0.78, 0.68, 0.91, and 0.74, respectively). Anti-dsDNA-NcX ELISA and anti-dsDNA CLIF assay had equally diagnostic performance (sensitivity, 66% vs. 68%, and specificity, 96% vs. 94%, respectively) whereas, anti-dsDNA LIA has low sensitivity (22%) but high specificity (100%). LIA, ELISA, and CLIF demonstrated comparable performance for the detection of specific antinuclear-antibodies. However, there were some discrepancy between assays particularly in the detection of anti-dsDNA antibody.

Current technologies for anti-ENA antibody detection: State-of-the-art of diagnostic immunoassays

BackgroundAutoantibodies against extractable nuclear antigens (ENA) play a pivotal role in the diagnosis and classification of systemic autoimmune rheumatic diseases (SARD). In recent years, newly developed methods have enabled the simultaneous and quantitative detection of multiple anti-ENA reactivities. However, data regarding the comparability of results obtained using different technologies across different platforms are scarce. In this study we compared eight different immunoassays, commonly used in current laboratory practice for detection of anti-ENA antibodies. MethodsSixty patients suffering from different SARD, 10 inflammatory arthritis patients (disease controls) and 10 healthy blood donors were included in this comparative study. Sera were collected in 15 centers belonging to the Study Group on Autoimmune Diseases of the Italian Society of Clinical Pathology and Laboratory Medicine. We evaluated the analytical sensitivity, specificity and diagnostic accuracy of each method for antibodies to Sm, RNP, Ro60, Ro52, Scl70, CENP-B and Jo1. Cohen's kappa was used to analyze the agreement among methods. ResultsAverage agreement among methods was 0.82, ranging from substantial (k = 0.72) to almost perfect (k = 0.92). However, while the specificity was very good for all methods, some differences emerged regarding the analytical sensitivity. ConclusionsDiagnostic performance of current technologies for anti-ENA antibody detection showed good comparability. However, as some differences exist among methods, laboratory scientists and clinicians must be aware of the diagnostic accuracy of the testing method in use.

Clinical spectrum time course in non-Asian patients positive for anti-MDA5 antibodies.

To define the clinical spectrum time-course and prognosis of non-Asian patients positive for anti-MDA5 antibodies. We conducted a multicentre, international, retrospective cohort study. 149 anti-MDA5 positive patients (median onset age 53 years, median disease duration 18 months), mainly females (100, 67%), were included. Dermatomyositis (64, 43%) and amyopathic dermatomyositis (47, 31%), were the main diagnosis; 15 patients (10%) were classified as interstitial pneumonia with autoimmune features (IPAF) and 7 (5%) as rheumatoid arthritis. The main clinical findings observed were myositis (84, 56%), interstitial lung disease (ILD) (108, 78%), skin lesions (111, 74%), and arthritis (76, 51%). The onset of these manifestations was not concomitant in 74 cases (50%). Of note, 32 (21.5%) patients were admitted to the intensive care unit for rapidly progressive-ILD, which occurred in median 2 months from lung involvement detection, in the majority of cases (28, 19%) despite previous immunosuppressive treatment. One-third of patients (47, 32% each) was ANA and anti-ENA antibodies negative and a similar percentage was anti-Ro52 kDa antibodies positive. Non-specific interstitial pneumonia (65, 60%), organising pneumonia (23, 21%), and usual interstitial pneumonia-like pattern (14, 13%) were the main ILD patterns observed. Twenty-six patients died (17%), 19 (13%) had a rapidly progressive-ILD. The clinical spectrum of the anti-MDA5 antibodies-related disease is heterogeneous. Rapidly-progressive ILD deeply impacts the prognosis also in non-Asian patients, occurring early during the disease course. Anti-MDA5 antibody positivity should be considered even when baseline autoimmune screening is negative, anti-Ro52 kDa antibodies are positive, and radiology findings show a NSIP pattern.

Connective Tissue Diseases on the Elderly Population in Dakar Hospital Setting

Introduction: Immunosenescence contributes to the development of auto-antibodies. However, while the prevalence of some autoantibodies increases with age, the incidence of connective tissue diseases decreases with age. This study aims to determine the clinical and paraclinical characteristics of connective tissue diseases in the elderly population. Materials and Methods: We conducted a retrospective and descriptive study, from March 2010 to March 2021, in the Internal Medicine Department of Aristide Le Dantec Hospital, including all the medical records of patients followed up for connective tissue disease and whose symptomatology began at an age greater than or equal to 65 years. Epidemiological, clinical, paraclinical, therapeutic and evolutionary data were collected from a pre-established survey form and then processed using SPSS software. Results: Overall, 22 cases were collected out of 275 seen on consultation. They involved 16 women and 6 men, aged between 65 and 85 years with a median of 70 years. The mean duration of the clinical picture was 15.7 months with extremes of 1 and 96 months. The clinical symptoms were joint pain in 21 patients associated with dry eye and mouth syndrome in seven cases and one patient underwent isolated dry eye and mouth syndrome. Joint involvement was deforming in 13 patients. Poor general condition was noted in 20 patients. Biology showed anemia in 14 patients, hyperleukocytosis (2 patients) and thrombocytosis (5 patients). The sedimentation rate (SR) was accelerated in 9 patients and the C-reactive protein (CRP) was positive in 12 patients. Immunology showed a positive Latex test (3 patients/6), Waaler-Rose reaction (8 patients/13), anti-cyclic citrullinated peptides (anti-CCP) antibodies (11 patients/11), anti-nuclear antibodies (2 patients/4). Anti-extractable nuclear antigens (anti-ENA) antibody testing in 4 patients showed positive anti-U1RNP (1 case), anti-SSA and anti-SSB (1 case). Plain X-Rays of the hands, wrists and feet showed destructive lesions in 16 patients. The diagnosis of rheumatoid arthritis (RA) was set in 21 patients, one of which was associated with Sjogren’s syndrome (SS) and one with primary Sjogren’s syndrome. Treatment was based on prednisone (21 cases), methotrexate (17 patients), and hydroxychloroquine (9 patients). The evolution was remarkable in 10 patients. Conclusion: Autoimmune diseases in the elderly are uncommon compared to the young adult population. In our study, we only found cases of rheumatoid arthritis and Sjogren’s syndrome. As the population ages, connective tissue diseases may be increasingly diagnosed.

Clinical Performance of Two Automated Immunoassays, EliA CTD Screen and QUANTA Flash CTD Screen Plus, for Antinuclear Antibody Screening.

BackgroundRecently, two fully automated immunoassays for antinuclear antibody (ANA) screening were introduced EliA CTD Screen (Thermo Fisher Scientific, Freiburg, Germany) and QUANTA Flash CTD Screen Plus (Inova Diagnostics, San Diego, USA). We evaluated their clinical performance in comparison with the indirect immunofluorescence assay (IIFA) and analyzed samples with discrepant results.MethodsIn total, 406 serum samples (206 from patients undergoing routine checkups and 200 from rheumatology clinic patients) were assayed using EliA, QUANTA Flash, and IIFA. We evaluated assay concordance and agreement and confirmed the presence of anti-extractable nuclear antigen (ENA) antibodies in samples with discrepant automated immunoassay and IIFA results. Additionally, we compared the clinical performance of each assay in diagnosing ANA-associated rheumatic disease (AARD) and adjusted the cut-off values.ResultsIn rheumatology clinic samples, the concordance and agreement were 91.5% and strong between EliA and QUANTA Flash, 79.0% and weak between EliA and IIFA, and 80.5% and moderate between QUANTA Flash and IIFA, respectively. In automated immunoassay-positive, IIFA-negative samples (N=15), all anti-ENA antibodies detected (6/15) were anti-Sjögren’s syndrome antigen A/Ro (Ro60) antibodies. The automated immunoassays and IIFA showed high accuracy for diagnosing AARD, and adjusted cut-off values improved their sensitivities (EliA with 0.56 ratio, 82.9% sensitivity; QUANTA Flash with 9.7 chemiluminescent units, 87.8% sensitivity).ConclusionsThe two automated immunoassays showed reliable performance compared with IIFA and can be efficiently used with the IIFA in clinical immunology laboratories. Clinical cut-off values can be adjusted according to the workflow in each laboratory.

ANA Pozitif Bireylerde ve ANA İlişkili Romatizmal Hastalıklarda Anti-DFS70 Antikorlarının ve DFS paterninin Değerlendirilmesi

Aim: In this study we aimed to find the frequency of anti-DFS70 antibodies and DFS pattern in ANA positive individuals and ANA associated rheumatic diseases (AARDs).Methods: In this study, 337 subjects who were evaluated in a rheumatology clinic with prediagnosis of rheumatic diseases with positive ANA test and had concurrent anti-extractable nuclear antigen (anti-ENA) antibodies results were retrospectively analyzed. Clinical diagnosis of patients and demographic characteristics were obtained from the patients' medical records.Results: A total of 337 subjects (305 women, 32 men) were included in this study. The mean age was 49.8 ± 14.2 years. Of the 337 participants, 111 (32.9%) had an IIF-DFS pattern and 226 (67.1%) had a non-DFS pattern. Anti-DFS70 antibodies were positive in 20.1% of individuals. Sixty eight individuals had AARDs. An IIF-DFS pattern was observed in 22.1% and a non-DFS pattern was observed in 77.9% of individuals with AARDs (p &amp;lt;0.05). Anti-DFS70 antibodies were positive in 13.2% of patients with AARDs. The frequency of AARDs was significantly lower in individuals with anti-DFS70 antibodies compared to individuals with other anti-ENAs antibodies (p &amp;lt;0.05).Conclusion: Anti-DFS70 antibodies may be present in patients with AARDs but AARDs are less prevalent in patients who had anti-DFS70 antibodies, compared with patients who had other anti-ENAs.

Autoantibody Profile of Egyptian Juvenile Systemic Lupus Erythematosus Patients and Its Association with Clinical Characteristics and Disease Activity.

ObjectiveThis study was conducted to estimate the frequency of anti-nuclear antibodies (ANAs), anti-dsDNA, and anti-extractable nuclear antigen (ENA) antibodies in juvenile systemic lupus erythematosus (JSLE) patients and their association with different clinical manifestations and disease activity.Patients and MethodsA cross-sectional study that includes 100 JSLE patients from Ain Shams University Hospital was conducted. All subjects underwent history taking, clinical examination, assessment of disease activity based on the SLE disease activity index (SLEDAI), laboratory investigations, and tests for autoantibodies, namely ANA, anti-dsDNA, and anti-ENA antibodies, including anti-Ro (SSA), anti-La (SSB), anti-Smith (Sm), and anti-U1-ribonucleoprotein (U1-RNP).ResultsThe most common clinical features were polyarthralgia (71%), haematological manifestations (65%), malar rash (54%), and nephritis (51%), respectively. All patients had positive ANA (100%), while anti-dsDNA frequency was 83%. The most common anti-ENA antibodies were anti-RNP (41%), anti-Sm (31%), anti-SSA (27%), and anti-SSB (20%), respectively. Anti-RNP had a clinical association with oral ulcer, Raynaud’ phenomena, haematological, neuropsychiatric and thromboembolic manifestations. Meanwhile, anti-Sm had a significant association with serositis, mucocutaneous, constitutional, and neuropsychiatric manifestations. Anti-SSA was associated with mucocutaneous, musculoskeletal, Raynaud’ phenomena, renal, haematological and cardiac manifestations, while anti-SSB was significantly associated with malar rash, serositis, thromboembolic, musculoskeletal, and neuropsychiatric manifestations. Concerning SLEADI score, anti-dsDNA antibody was significantly associated with moderate disease activity score (p=0.032) while anti-SSA significantly associated with high disease activity (p=0.045). Both anti-SSB and anti-Sm were significantly associated with both moderate and high disease activities, meanwhile anti-U1-RNP was associated with moderate disease activity (p=0.014).ConclusionAnti-dsDNA and anti-ENAs antibodies were frequently found in JSLE patients (83%, 63%), respectively. They were significantly associated with variable clinical manifestations and could be used as predictors for assessment of disease activity.

Niveles de interferón tipo I en pacientes con lupus eritematoso sistémico

Introduction: type I interferon (IFN) is a cytokine that plays a fundamental role in the pathogenesis of Systemic Lupus Erythematosus (SLE). Different levels of this cytokine could explain the heterogeneity of this pathology and be useful to evaluate its activity. Objectives: to determine the serum type I IFN levels in patients with SLE and evaluate its usefulness as a biomarker of activity. Material and Method: 16 patients with SLE (ACR 1997) and 16 controls. Methods: Disease activity (SLEDAI-2K), organ damage (SLICC), type I IFN (HEK-Blue- IFNα/β), anti-dsDNA antibodies (Indirect Immunofluorescence), anti-ENA antibodies (ELISA), C3-C4 (Immunoturbidimetry). Statistics: InfoStat/Instat/MedCalc. P values &lt;0.05 were statistically significant. Results: an increase in IFN concentration was observed in the SLE group respect to the control (p &lt;0.05). Patients with IFN values above the cut-off point were associated with the presence of anti-dsDNA antibodies (OR: 13.33; p&lt;0.05). Hypocomplementemic patients and those with a SLEDAI-2K score greater than 8 had higher IFN levels compared to patients with normal complement and a lower index score, respectively (p&lt;0.05). Conclusions: these results suggest the importance that the determination of IFN type I could have for the monitoring of SLE activity.

Early Intervention and Resolution of Pediatric Intestinal Pseudo-Obstruction in Systemic Lupus Erythematosus: A Pediatric Case Report

Early Intervention and Resolution of Pediatric Intestinal Pseudo-Obstruction in Systemic Lupus Erythematosus: A Pediatric Case Report

Serum uric acid as a sensitive concordant marker with lupus nephritis and new onset of renal damage: a prospective cohort study.

The objectives of this study are to assess serum different uric acid levels among systemic lupus erythematosus patients with or without active lupus nephritis in comparison to healthy controls and to study the relation of baseline uric acid levels to the development of new-onset renal damage in lupus nephritis. This is a case-control study followed by a prospective cohort of systemic lupus erythematosus (SLE) patients. Three groups were included; all were having normal kidney function, 25 SLE patients with recently diagnosed active lupus nephritis (LN), 26 SLE patients without LN, and 38 healthy controls. Serum uric acid (SUA)and serum creatinine were done for all groups; for SLE patients, 24-h protein in the urine, urinalysis, C3, C4 levels, anti-DNA, anti-ENA antibodies, SLE Disease Activity Index (SLEDAI), and SLICC/ACR damage index (SDI) evaluation were also calculated. Follow-up was done with clinical and laboratory assessment including SUA, with SLEDAI and SDI evaluation. Serum uric acid was significantly higher in SLE patients with active LN than the other two groups (p < 0.05), a cutoff value of serum uric acid associated with lupus nephritis onset was 0.41 mmol/L with a sensitivity of 58% and specificity of 100%, however, C3 and C4 showed very low sensitivity and specificity. During follow-up, all patients with LN with baseline serum uric acid ≥ 0.52 mmol/L were associated with new-onset renal damage within 43 months. High-serum uric acid levels showed a significant association with lupus nephritis onset and new onset of renal damage. Key Points • Serum uric acid is a cheap, rapid, and popular test available in most of the worldwide laboratories; its higher levels showed a significant association with lupus nephritis onset and new onset of renal damage • The current work is the largest study done on lupus nephritis with strict control to the confound risk factors that are associated with the increase of the uric acid levels; moreover, it is the first study to assess such relation in Saudi population • Uric acid could have a role in the pathogenesis of lupus nephritis patients and consequent renal damage.

The Effect of Proteinuria on Antinuclear Antibody Assay Results in Patients with Glomerulonephritis

Background:Glomerulonephritis mostly results from dysregulated immune system. Impaired immune mechanisms can be primary or secondary to an autoimmune disorder. Antinuclear antibodies (ANA) are hallmark of autoimmunity and are frequently present at high titer (≥ 1: 160). ANA are characterized via anti-double stranded deoxyribonucleic acid (dsDNA) and antiextractable nuclear antigen (ENA) antibodies for the identification of underlying autoimmune disease. Heavy proteinuria can affect assessment of autoantibodies hence special attention is required for the definitive diagnosis in such cases.Objective:Our aim was to determine impact of heavy proteinuria on ANA titer, anti-dsDNA and anti-ENA antibodies in glomerulonephritis patients.Methods:150 glomerulonephritis patients were enrolled in this study. All had antinuclear antibodies, samples were tested for anti-dsDNA and anti-ENA. ANA titer of ≥1:160 was taken significant. Proteinuria was assessed by spot protein/creatinine ratio. Data was analyzed using SPSS software version. 20Results:Heavy proteinuria was present in 119(79%) patients. Low ANA titer(≤1:80) was present in 37(25%) patients. Of 33 patients with heavy proteinuria and low ANA titer, ANA was characterized in 11 patients. These include anti-dsDNA(two), anti-SSA(four), anti-Sm (one), antihistones( one), anti-RNP(two), anti-Pm-Scl(one) and anti-ribosomal P protein (two).There was no significant difference in the prevalence of various autoantibodies in patients with high or low ANA titer with heavy proteinuria.Conclusion:This study highlights the importance of low ANA titer in glomerulonephritis patients in the setting of heavy proteinuria. Significant protein loss may alter actual titer of autoantibodies. Hence in this scenario clinically correlation along with ANA characterization via specific autoantibodies is required for adequate patient management.

Pancytopenie, panhypopituitarizmus a jaterní cirhóza: rozbor složité kazuistiky

Panhypopituitarism following craniopharyngioma resection has systemic impact with potential influence on physio-logical hematopoiesis. There is a growing body of evidence of liver fibrosis/cirrhosis risk development due to altered metabolism and lipid accumulation. The authors present a case report of a woman with a history of craniopharyngioma resection followed by aggravating pancytopenia with suspected indolent lymphoproliferative disorder and possible acquired bone marrow aplasia syndrome due to paroxysmal nocturnal hemoglobinuria. A complex hemostasis disorder with deficiency of multiple coagulation factors (FXII, FXI, FX, FIX, FVII, FX, FV, FXIII, antitrombin, protein C, protein S) was accidentally detected. Despite normal sonographic liver imaging, all possible causes of chronic liver disease were systematically excluded (viral hepatitis, hemochromatosis, Wilson´s disease, &#945;-1-antitrypsin deficiency); anti-LKM-1 and anti-ENA antibodies were detected. Finally, the magnetic resonance imaging confirmed image of liver cirrhosis - with signs of portal hypertension.

Only monospecific anti-DFS70 antibodies aid in the exclusion of antinuclear antibody associated rheumatic diseases: an Italian experience.

Background The dense fine speckled (DFS) is one of the most common patterns that can be observed as a result of the anti-nuclear antibodies (ANA) test on HEp-2 cells and is mostly caused by antibodies to DFS70 as the main antigenic target. As was recently demonstrated, isolated anti-DFS70 positivity can be used as an aid in the exclusion of ANA associated rheumatic diseases (AARD) due to the opportunity to better interpret unexplained positive IIF ANA results. Methods Our study included 333 subjects with AARD, 51 undifferentiated connective tissue disease (UCTD) patients, 235 disease controls and 149 healthy blood donors from an Italian cohort. All samples were tested for anti-DFS70 and anti-ENA antibodies using QUANTA Flash assays (Inova Diagnostics, San Diego, CA, USA). Results No differences in the prevalence of anti-DFS70 antibodies were seen among AARD, non-AARD and UCTD (2.1% [7/333] vs. 2.3% [9/384] vs. 5.9% [3/51], respectively; p-value = 0.188). AARD patients positive for anti-DFS70 antibodies showed in all cases an accompanying anti-ENA specificity. In contrast, monospecific anti-DFS70 antibodies showed a significantly different distribution with a clear trend across the main groups (AARD vs. non-AARD vs. UCTD: 0% [0/7] vs. 22% [2/9] vs. 100% [3/3], p = 0.007). Anti-DFS70 antibody levels among AARD, non-AARD and UCTD patients were not significantly different (p = 0.094). Within the anti-DFS70 antibody positive cases, AARD cohort showed a higher variability (median [min-max]: 3.2 [3.2-450.8] CU) compared to non-AARD (median [min-max]: 3.2 [3.2-75.7] CU) and UCTD patients (median [min-max]: 3.2 [3.2-59.0] CU). Conclusions Our preliminary data showed a similar frequency of anti-DFS70 antibodies in AARD, UCTD and non-AARD cohorts. Monospecificity of anti-DFS70 antibodies but not their mere presence is the key element in the diagnostic algorithm. Mono-specific anti-DFS70 antibodies might be a helpful biomarker to discriminate individuals with AARD from non-AARD presenting with a positive ANA.

Diagnostic Utility of Separate Anti-Ro60 and Anti-Ro52/TRIM21 Antibody Detection in Autoimmune Diseases.

Anti-SS-A antibodies are often sought for in autoimmune diseases diagnosis. Two different target proteins have actually been identified: Ro52 and Ro60. Clinical and immunological associations seem different depending on anti-Ro52 or anti-Ro60 antibodies presence. However, due to a heterogeneous presentation in the literature, some immunology laboratories in France have stopped providing anti-Ro52 antibody findings. We report here a new hospital study designed to determine the diagnostic utility of the separate detection of anti-Ro52 and anti-Ro60 antibodies. We conducted a retrospective, observational study, including every adult patient with positive antinuclear antibodies (ANA) tested in our immunology laboratory, and associated with anti-Ro52 and/or anti-Ro60 antibodies, between 2011 and 2014. Out of 13032 sera tested for ANA, 399 adults had antibodies to Ro52 and/or Ro60; 81.7% were female, with a mean age of 54.5 ± 17.0 years. Anti-Ro52 antibodies were found in 75.7% of the patients and anti-Ro60 antibodies in 56.9%. Among them, 43.1% were classified in the Ro52 + Ro60- group, 32.6% in the Ro52 + Ro60 + group and 24.3% in the Ro52-Ro60+ group. In the Ro52-Ro60+ group, systemic lupus was the most frequent diagnosis (48.5%), with a possible association with antiphospholipid antibodies (anti-cardiolipin antibodies: OR 2.5 (CI95 [1.0–5.0], p = 0.05) and lupus anticoagulant {OR 3.6 (CI95 [1.10–10.0] p = 0.02)}. In the Ro52+Ro60+, primary Sjögren Syndrome was the most likely (OR 4.2 95% CI [2.1–8.3] p < 10−4), especially in patients Ro52+Ro60+La+. Patients with isolated anti-Ro52 had a wider variety of diseases associated, but among auto-immune diseases they were more prone to inflammatory myositis (OR 10.5 [1.4–81.7], p = 0.02) and inflammatory rheumatism (OR 4.6 [1.6–13.8], p = 0.006) in contrast to systemic lupus (OR 0.2 [0.1–0.3], p < 10−4) or primary Sjögren's syndrome (OR 0.1 [0.06–0.2], p < 10−4). We therefore suggest that, when anti-ENA antibodies are prescribed, it should include separate anti-Ro52 and anti-Ro60 antibodies determination. To go even further, we would like to suggest a change in ENA nomenclature to avoid confusion, abandoning the anti-SS-A label in favor of the anti-Ro52/TRIM21 or anti-Ro60 antibody for a clearer designation.

Autoantibody Profile and Its Association with Clinical Presentation of Paediatric SLE Patients

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of various auto antibodies including anti-nuclear antibody, double stranded DNA and antibodies to extractable nuclear antigens (ENA), which include four groups of RNA binding protein namely Sm, RNP, SSA/Ro and SSB/La. The objectives were to detect the frequency and pattern of ANA, frequency of anti- ENA antibodies and association between the clinical presentations with ANA and Anti-ENA antibodies in paediatric SLE patients. It was a cross sectional study and the data was collected from patients fulfilling the ACR 1997 revised criteria of SLE in the Department of Paediatrics, BSMMU, Dhaka, Bangladesh. Among 50 paediatric SLE patients, ANA was positive in 94% of the patients. Homogenous pattern of ANA was the highest (57%) followed by speckled (31%), cytoplasmic (6.6%) and nucleolar (3.3%) patterns. Anti-ds DNA positivity was 86% and anti-ENA positivity was 56% in this study. Among them, anti–RNP was found in 43.5% followed by anti-sm (24%), anti-SSA (24%) and anti-SSB (17%). Anti–RNP antibody was associated with renal and gastrointestinal and Anti–SSA was associated with only gastrointestinal manifestations. ANA, anti ds-DNA, anti ENA positivity were found significantly among paediatric SLE patients and clinical presentation of them had association with Anti-ENA antibodies.