anti-Ro Research Articles

Association of anti-Ro52, anti-Ro60 and anti-La antibodies with diagnostic, clinical and laboratory features in a referral hospital in Jerez, Spain

ObjectiveSeveral antibodies have proven to be useful in autoimmune diseases, as markers for diagnosis, prognosis or clinical manifestations. Our objective was to evaluate the diagnosis and manifestations associated for antibodies anti-Ro52, anti-Ro60 and anti-La at a referral hospital in Spain. MethodsWe retrospectively analyzed the antigenic specificities of the consecutive samples submitted to the Immunology Unit for antinuclear antibody screening between 2002 and 2012. We included patients with more than one positive sample for some of the autoantibodies anti-Ro52, anti-Ro60 or anti-La. We also reviewed diagnosis, clinical and laboratory features. As dependent variable we evaluated possible combinations of anti-Ro52, anti-Ro60 and anti-La. Results322 patients, 91% females, were studied (age 44.3±15.51 years). The most frequent diagnosis was Sjögren's syndrome (40.06%) and systemic lupus erythematosus (SLE) (36.6%). The most prevalent pattern by indirect immunofluorescence was the fine speckled (69.9%). Anti-Ro52+/anti-Ro60+/anti-La+ combination was positively associated with fine speckled pattern (p: 0.001) and negatively with homogeneous (p: 0.016) and cytoplasmic pattern (p: 0.002). Isolated anti-Ro52+ was negatively associated with fine speckled pattern (p<0.001) and positively with the cytoplasmic one (p<0.001). The main positive associations with clinical symptoms were xerostomia and xerophthalmia with anti-Ro52+/anti-Ro60+/anti-La+ (p<0.001), oral ulcers with anti-Ro52+/anti-Ro60+/anti-La− (p: 0.002) and alopecia with anti-Ro52−/anti-Ro60+/anti-La− (p: 0.003). Negative associations were xerophthalmia and photosensitivity with anti-Ro52+/anti-Ro60−/anti-La− (p: 0.003). Laboratory positive associations were hypergammaglobulinemia with anti-Ro52+/anti-Ro60+/anti-La+ (p: 0.003), and hypocomplementemia with anti-Ro52−/anti-Ro60+/anti-La− (p: 0.003). Leucopenia was negatively associated with anti-Ro52+/anti-Ro60−/anti-La− (p: 0.003). ConclusionOur study found significant relationships between clinical and laboratory manifestations with different patterns of antibodies to anti-Ro52, anti-Ro60 and anti-La. The combination of antibodies might be clinically useful due to prognostic and therapeutic implications.

Renal Thrombotic Microangiopathy in Proliferative Lupus Nephritis: Risk Factors and Clinical Outcomes: A Case-Control Study.

Renal thrombotic microangiopathy (TMA) may be associated with lupus nephritis. Its relationship to other disease factors and its specific effect on prognosis are not precisely known. Evidence regarding these aspects is controversial, and information focusing on kidney-limited TMA in systemic lupus erythematosus (SLE) patients is scarce. The aims of this study were to identify risk factors for renal TMA in patients with lupus nephritis and to determine its impact on clinical outcomes. A case-control study was performed. We studied 245 renal biopsies from SLE patients. We included patients with renal TMA, as well as control subjects adjusted for glomerulonephritis class, estimated glomerular filtration rate, activity and chronicity indices, and follow-up time. Serological and clinical features were measured at the time of the biopsy and during follow-up. Twenty-three patients with renal TMA and 21 control subjects were included. There were no differences in Systemic Lupus Erythematosus Disease Activity Index score, end-stage renal disease, or mortality between groups during follow-up. After multivariate analysis, lymphopenia (odds ratio, 10.69; 95% CI, 1.35-84.74) and anti-Ro antibody positivity (odds ratio, 8.96; 95% CI, 1.49-53.57) remained significantly associated with renal TMA. Lymphopenia and anti-Ro positivity are independent risk factors for renal TMA in SLE patients. This increased risk could be a consequence of the potential role of these factors in endothelial dysfunction and damage. Outcomes were similar for patients with the same estimated glomerular filtration rate and biopsy characteristics, regardless of the presence of TMA.

Induction of autoimmune response to the extracellular loop of the HERG channel pore induces QTc prolongation in guinea-pigs.

Channelopathies of autoimmune origin are novel and are associated with corrected QT (QTc) prolongation and complex ventricular arrhythmias. We have recently demonstrated that anti-SSA/Ro antibodies from patients with autoimmune diseases and with QTc prolongation on the ECG target the human ether-à-go-go-related gene (HERG) K+ channel by inhibiting the corresponding current, IKr , at the pore region. Immunization of guinea-pigs with a peptide (E-pore peptide) corresponding to the extracellular loop region connecting the S5 and S6 segments of the HERG channel induces high titres of antibodies that inhibit IKr , lengthen the action potential and cause QTc prolongation on the surface ECG. In addition, anti-SSA/Ro-positive sera from patients with connective tissue diseases showed high reactivity to the E-pore peptide. The translational impact is the development of a peptide-based approach for the diagnosis and treatment of autoimmune-associated long QT syndrome. We recently demonstrated that anti-SSA/52kDa Ro antibodies (Abs) from patients with autoimmune diseases and corrected QT (QTc) prolongation directly target and inhibit the human ether-à-go-go-related gene (HERG) K+ channel at the extracellular pore (E-pore) region, where homology with SSA/52kDa Ro antigen was demonstrated. We tested the hypothesis that immunization of guinea-pigs with a peptide corresponding to the E-pore region (E-pore peptide) will generate pathogenic inhibitory Abs and cause QTc prolongation. Guinea-pigs were immunized with a 31-amino-acid peptide corresponding to the E-pore region of HERG. On days 10-62 after immunization, ECGs were recorded and blood was sampled for the detection of E-pore peptide Abs. Serum samples from patients with autoimmune diseases were evaluated for reactivity to E-pore peptide by enzyme-linked immunosorbent assay (ELISA), and histology was performed on hearts using Masson's Trichrome. Inhibition of the HERG channel was assessed by electrophysiology and by computational modelling of the human ventricular action potential. The ELISA results revealed the presence of high titres of E-pore peptide Abs and significant QTc prolongation after immunization. High reactivity to E-pore peptide was found using anti-SSA/Ro Ab-positive sera from patients with QTc prolongation. Histological data showed no evidence of fibrosis in immunized hearts. Simulations of simultaneous inhibition of repolarizing currents by anti-SSA/Ro Ab-positive sera showed the predominance of the HERG channel in controlling action potential duration and the QT interval. These results are the first to demonstrate that inhibitory Abs to the HERG E-pore region induce QTc prolongation in immunized guinea-pigs by targeting the HERG channel independently from fibrosis. The reactivity of anti-SSA/Ro Ab-positive sera from patients with connective tissue diseases with the E-pore peptide opens novel pharmacotherapeutic avenues in the diagnosis and management of autoimmune-associated QTc prolongation.

Cutaneous characteristics and association with antinuclear antibodies in 402 patients with different subtypes of lupus erythematosus.

Lupus erythematosus (LE) is an autoimmune disease characterized by a heterogeneous spectrum of skin manifestations and organ affection, and is frequently associated with serum autoantibodies, which mostly remain positive through the course of the disease. The classification of LE is still a controversial topic. To examine the prevalence and long-term course of autoantibodies in patients with cutaneous LE (CLE) and/or systemic LE (SLE) treated in the outpatient clinic for connective tissue diseases of the department of Dermatology in Bochum, Germany. Four hundred and two patients with LE were evaluated for antinuclear antibodies at a whole of 1572 time points. The prevalence as well as the long-term positivity of antinuclear antibodies and their correlation with the various subtypes of disease was examined. Antinuclear antibody (ANA) testing and anti-ds-DNA antibodies were not only more prevalent in SLE patients (as expected from the ACR criteria for diagnosis of SLE, P < 0.0001), but also have had a more consistent course in the long-term evaluation (P = 0.0001 and P = 0.0111 respectively). Subacute cutaneous LE (SCLE) was associated with ANA (P = 0.0075), anti-Ro (P < 0.0001) and anti-La (P < 0.0001) antibodies, showing also higher consistency rates for these antibodies than discoid LE (DLE, P = 0.049, P = 0.004, P = 0.0004). Our data from 100 patients with LE tumidus (LET) support its perception as a distinct subtype of LE, not correlating with systemic disease or antinuclear antibodies (P < 0.0001). Anti-U1-ribonucleoprotein antibodies correlated with CLE in SLE patients (P = 0.0237), whereas non-LE-specific antinuclear antibodies were a rare, inconsistent autoimmune epiphenomenon in patients with SLE. Long-term analysis of antinuclear antibodies has shown significant differences in various clinical subtypes of LE, confirming the actual classification of the disease. A serial evaluation of antinuclear antibodies may support the classification of disease in LE patients with overlapping clinical features.

A study of the influence of ethnicity on serology and clinical features in lupus.

The objective of this study was to review the links between ethnicity, serology and clinical expression in systemic lupus erythematosus (SLE) in a single cohort that was followed over a 36-year period. Patients with SLE treated at the University College London Hospitals (UCLHs) between January 1978 and December 2013 formed the cohort. We assessed the demographic, clinical and serological data. Standard methods were used for laboratory testing. The Student t test and Mann-Whitney U test were used for the continuous variables; the Fisher's exact test was used for the categorical variables. We studied 624 SLE patients: There were 571 women (91.5%), with a mean age at diagnosis of 29.0 ± 6.5 years; and 53 men (8.5%), with a mean age at diagnosis of 29.4 ± 15.3 years. Ethnically, 369 of the patients were European, 100 were Afro-Caribbean, 77 were East Asian, 56 were South Asian and 21 were of mixed ethnicity. The East Asian patients developed the disease at a younger age than the other ethnic groups (p < 0.0001). The Afro-Caribbean patients were less frequently associated with the presence of rash and photosensitivity, and the non-European patients were more likely to have alopecia and renal involvement. The South Asian patients were significantly associated with musculoskeletal and neurological involvement, serositis, Sicca syndrome and hematological features. The Afro-Caribbean patients had the highest prevalence of anti-Smith, anti-RNP, anti-Ro and anti-La antibodies. Anti-IgG anticardiolipin (aCL) antibodies were significantly associated with the non-East Asian groups; and hypocomplementemia was common in the East Asians. Rash, alopecia, mouth ulcers, serositis, neurological, joint and renal involvement were significantly associated with the presence of anti-Smith and anti-RNP antibodies in the Afro-Caribbean group. We also observed an association of joint involvement and the presence of anti-Ro and anti-La antibodies in this group. The East Asian patients developed their SLE disease at a younger age than the other ethnic groups. Cutaneous involvement was more frequent in those who were not Afro-Caribbean. Serositis, joint and neurological involvement were more frequently diagnosed in the South Asian patients. Anti-ENA antibodies were frequently associated with the Afro-Caribbean patients.

Rituximab in the Treatment of Jo1 Antibody-associated Antisynthetase Syndrome: Anti-Ro52 Positivity as a Marker for Severity and Treatment Response.

Rituximab (RTX) has been used successfully for the treatment of severe Jo1 antibody-associated antisynthetase syndrome. The aim of this retrospective study was to evaluate the effect of RTX in severe Jo1 antisynthetase syndrome and determine predictive factors for response. There were 61 patients with Jo1 antisynthetase syndrome identified; 18 of these received RTX. One patient was lost to followup. The remaining 17 patients and 30 out of 43 patients who were treated with conventional immunosuppressive (IS) drugs were followed for a mean of 35 months and 84 months, respectively. Polymyositis/dermatomyositis (95%) and interstitial lung disease (ILD; 66%) were the dominant clinical manifestations. Detection of anti-Ro52 antibodies (43%) was significantly associated with acute-onset ILD (p = 0.016) with O2 dependency, and patients with high concentrations of anti-Ro52 (20%) had the highest risk (p = 0.0005). Sixteen out of 18 patients (89%) showed a fast and marked response to RTX. Among those patients who were highly positive for anti-Ro52, response to RTX was seen in 7 out of 7 cases (100%), but no response to cyclophosphamide (n = 4), cyclosporine A (n = 3), azathioprine (n = 9), methotrexate (n = 5), or leflunomide (n = 2) was observed. One patient treated with RTX died of pneumonia. RTX is effective in the treatment of severe forms of Jo1 antisynthetase syndrome. In our retrospective study, the presence of high anti-Ro52 antibody concentrations predicts severe acute-onset ILD and nonresponse to IS drugs. In contrast to conventional IS, RTX is equally effective in patients with Jo1 antisynthetase syndrome, independent of their anti-Ro52 antibody status.

Lupus T and B cell cross-reactivity between the human Ro60 autoantigen and Ro60 orthologs from the human microbiota

Abstract Human Ro60 is an RNA binding protein that is commonly targeted in systemic autoimmunity. We identified Ro60 orthologs that are conserved in a subset of skin, oral, and gut commensal species. Since anti-Ro60 antibodies are the earliest autoantibodies detected in lupus patients, we hypothesized that commensal Ro60 orthologs may trigger autoimmunity via autoepitope cross-reactivity in genetically susceptible individuals. While Ro60-producing gut commensals were common among both healthy controls and lupus patients, only antibodies from 4 Ro60-positive lupus patients, but not Ro60-negative subjects, co-immunoprecipitated Ro60 and its bound Y RNA from the Ro60-containing skin commensal P. propionicum. This suggests antibody cross-reactivity between human Ro60 antibodies and commensal Ro60. Next, Ro60-specific CCR6+ and CCR6- CD4 memory T cells clones from lupus patients were generated using a T cell library assay. Ro60 CCR6+ T cell clones proliferated in response to P. propionicum, demonstrating T cell cross-reactivity with commensal Ro60. Finally, germ-free mice monocolonized with B. thetaiotaomicron, a Ro60 ortholog-containing gut commensal, produced fecal anti-human Ro60 IgA antibodies (n=4, p=0.04), linking anti-Ro60 commensal responses in vivo with the generation of human Ro60 autoantibodies. In summary, Ro60 autoimmune T and B cells from human lupus patients cross-reacted with commensal Ro60 in vitro and commensal Ro60 triggered anti-Ro60 antibodies in vivo. Taken together, these data suggest that colonization with autoantigen ortholog-carrying species may sustain chronic autoimmunity in patients. This concept could lead to development of novel therapeutic approaches targeted at the human microbiota.

A potential link between immune response to a periodontal bacterium, Aggregatibacter actinomycetemcomintans and Systemic Lupus Erythematosus

Abstract Infections are a significant cause of morbidity in Systemic Lupus Erythematosus (SLE). Although oral health is considerably compromised in SLE patients, the role of oral pathogens in influencing lupus pathogenesis is not known. In the present study, antibody responses to a periodontogenic, facultative anaerobic bacterium, Aggregatibacter actinomycetemcomitans (Aa), (which serve as an indicator of past or ongoing infection with Aa), were measured in SLE patients (n=587) and healthy controls (n=75). The associations between anti-Aa antibody titers and clinical measures of SLE were evaluated. The effect of Aa infection on development of lupus was investigated in the NZM2328 mice. The ability of Aa to induce neutrophil extracellular traps (NETs) was studied in vitro. Both SLE patients and controls showed the presence of anti-Aa. In SLE patients, the anti-Aa titers correlated strongly with anti-dsDNA, anti-chromatin, anti-RNP, and anti-Sm; but not with anti-Ro52, anti-Ro60, and anti-La antibodies. NZM2328 mice developed a robust immune response to Aa, and the Aa infection caused an accelerated onset of autoantibody and renal disease. In addition, Aa readily induced NETosis in NZM2328 neutrophils. Our data suggest for the first time that SLE patients are exposed to oral pathogen Aa, and this exposure significantly influences immune responses against a subset of lupus-associated autoantigens, possibly through NETosis. Furthermore, our studies suggest that management of oral health in SLE patients might prove to be beneficial for controlling lupus.

Is peripheral paraneoplastic neurological syndrome possible in primary brain tumors?

IntroductionSystemic malignant diseases cause the induction of autoimmunity, for example, paraneoplastic syndromes. There are no proofs of paraneoplastic syndromes in primary brain tumors. The aim of the study was to evaluate the involvement of the peripheral nervous system, together with an assessment of onconeuronal and antineural antibodies as indicators of humoral immune response against nervous system in patients with primary brain tumors.Materials and MethodsClinical examinations, electrophysiological studies of peripheral nerves (motor and sensory conduction velocity studies, conduction velocity distribution tests, thermal and vibratory quantitative sensory tests, and sympathetic skin response tests) and muscles, blood sampling collection (assessment of onconeuronal, and antineural antibodies) were performed on 33 patients with newly recognized primary brain tumors within 2–4 days after their admission to our department.ResultsWe revealed statistically significant changes of peripheral nerves, more pronounced in the peroneal nerve in standard and conduction velocity distribution tests, as well as in sympathetic skin responses. We revealed significantly higher vibratory thresholds, and pain thresholds for cold and warm in the upper and lower limbs in the study group than in the controls. In five patients, we have identified anti‐neuroendothelium, anti‐GFAP, anti‐MAG, anti‐PCNA, and anti‐Ro52 antibodies.ConclusionsIn patients with primary brain tumors, electrophysiological changes in peripheral nerves, together with the presence of the antineural antibodies suggest an autoimmune humoral response, and make the diagnosis of paraneoplastic neurological syndrome possible.

Outcome of 69 Pregnancies within a Multinational Population with Systemic Lupus Erythematosus in Qatar

The aim of this study is to determine the frequencies of abnormal pregnancy outcomes in a cohort of patients with systemic lupus erythematosus (SLE). Data of 69 pregnancies of 37 SLE patients were analyzed retrospectively. Lupus activity was assessed based on SLE Disease Activity Index (SLEDAI) criteria. Compared with pregnancies without Lupus nephritis (LN), pregnancies with LN were associated with a higher risk of still birth (p=0.092), higher rate of eclampsia (p=0.103), intrauterine growth restriction (IUGR) (p=0.556), and pregnancy induced hypertension (PIH) (p=0.412). PIH (17.4% vs 11.1%), IUGR (34.7% vs 11.8%), preterm delivery (26.1 % vs 11.8%), still birth (13% Vs 5.6%) and eclampsia (13% Vs 0%), all were observed to be higher in active lupus patients compared to those in remission. However, these differences were not statistically significant (p>0.05). Absence of LN, proteinuria and low complement component 3 (C3) were potential (p<0.15) predictors for live births. Anti-Ro antibodies, high anti-double stranded DNA antibody (anti-dsDNA), and low C3 were strongly associated with pre-term live births and Anti-Ro antibodies was significantly associated with IUGR. In conclusion SLE in pregnancies in a multinational population in Qatar was associated with higher adverse pregnancy outcomes. Disease activity during pregnancy, proteinuria, LN and eclampsia/preeclampsia were all negatively associated with pregnancy outcome such as IUGR, still births and preterm delivery. Laboratory parameters such as presence of Anti Ro/La antibody and low level of C3 were also associated with adverse pregnancy outcome.

Comparison of antibody assays for detection of autoantibodies to Ro 52, Ro 60 and La associated with primary Sjögren's syndrome

Anti-Ro(52/60) and anti-La constitute the hallmark autoantibodies in primary Sjögren's syndrome, being present in 40–70% of sera. Several anti-Ro/La assays exist, but antibody detection appears to be assay-specific, thus the aim of this study was to compare several anti-Ro/La assays. In total, 96 sera from individuals with primary Sjögren's syndrome and 114 healthy controls were tested for anti-Ro 52/60 and anti-La in 17 immunoassays.Especially the immunoassays used for detection of anti-Ro 52 differed in their sensitivity (48–79%), while only small differences in sensitivities were observed for the anti-Ro 60 (69–77%) anti-La (39–44%) assays. Concordances of 65%, 79% and 73% for the anti-Ro 52, anti-Ro 60 and anti-La assays were found, respectively. The majority of the assays yielded high specificities, primarily ranging from 97 to 100%, except from a single anti-Ro 60 assay, which yielded a specificity of 79%. Occasionally, reactivity levels were increased in a few assays, indicating that false-positive results can be obtained when applying assays of reduced specificity. In general, the commercial assays appeared to perform better than the in-house analyses. When correcting the in-house assays for background reactivity, sensitivities were reduced by approximately 7%, 17%, and 19% for anti-Ro 52, anti-Ro 60 and anti-La assays, respectively, illustrating the pitfalls when applying immunoassays for detection of autoantibodies, which in theory may apply to commercial assays as well. Finally, increased total sensitivities were obtained when combining assays.These studies contribute to clarify the clinical utility of immunoassays for detection of autoantibodies of Ro 52, Ro 60 and La and illustrate that the most efficient strategy to maximize antibody sensitivity is to combine several assays.

Maternal autoantibody profiles at risk for autoimmune congenital heart block: a prospective study in high-risk patients

ObjectiveThis prospective study aimed to identify antibody profiles characterising mothers with fetuses developing congenital heart block (CHB) by comparing their antibody frequencies and levels with those in unaffected mothers.MethodsEighty-one consecutive...

Subclinical myocardial impairment in SLE: insights from novel ultrasound techniques and clinical determinants.

Myocardial damage is frequent and often silent in systemic lupus erythematosus (SLE). The aim of the study was to determine the prevalence of myocardial damage by novel ultrasound techniques and to systematically assess the relationship between subclinical cardiac dysfunction and SLE-related clinical parameters. Seventy-five consecutive SLE patients without evidence of cardiac disease and seventy-three controls underwent standard transthoracic echocardiography using classical and novel ultrasound techniques: tissue Doppler imaging and speckle tracking echocardiography. Patient characteristics, cumulative organ damage and laboratory data were retrieved by medical chart review. Within the cohort, 89.3% of the patients were female; mean+/-SD age and median (IQR) disease duration were 43.2+/-12.5 years and 8.03(6.3) years, respectively. SLE patients exhibited a significant decrement in endocardial longitudinal strain (-18.4% vs 19.3%, p=0.001) compared with controls. Diastolic dysfunction was detected in 34 (45.3%) of SLE patients. Major determinants of systolic and diastolic dysfunction were hypertension (p=0.023 and p<0.001, respectively), associated antiphospholipid syndrome (APS) (p<0.001 and p<0.001, respectively), cumulative damage accrual (p<0.001 and p=0.003, respectively), and disease duration (p=0.03 and p<0.001, respectively). Notably, anti-Ro antibodies were present in 37% of the SLE patients who had better systolic longitudinal performance. Neither disease activity, nor specific organ involvement, were associated with myocardial impairment. Systolic longitudinal and diastolic performance impairments are frequent findings in SLE patients without overt cardiovascular disease. Cumulative organ damage, disease duration, APS, and hypertension are major determinants for early heart involvement in SLE patients.

A patient with subacute cutaneous lupus erythematosus along Blaschko lines: Implications for the role of keratinocytes in lupus erythematosus

Abstract Blaschko lines are manifestations of cutaneous mosaicism, with apparent contrast between normal cells and abnormal cells, which carry postzygotic mutations. Linear cutaneous lupus erythematosus is a rare subset of cutaneous lupus erythematosus (CLE), characterized by skin lesions along Blaschko lines. In this paper, we presented a 47-year-old female with subacute CLE lesions along Blaschko lines. Although the antinuclear antibody and anti-Ro titers were remarkably high, there were no systemic symptoms. The histopathology showed atrophic epidermis with vacuolization of basal keratinocytes and papillary edema. While no typical linear lupus band was found, the direct immunofluorescence revealed cytoid bodies with immunoglobulin G, immunoglobulin M, C3, and C4 depositions in the papillary dermis. The skin lesions completely resolved after topical tacrolimus treatment, and the clinical course was 10 months without recurrence. We reviewed the literature and summarized that CLE along Blaschko lines supports the functional role of Ro antigens and keratinocytes in the development of CLE.

Stevens-Johnson Syndrome-Like Skin Lesions in a Patient with Juvenile Systemic Lupus Erythematosus.

Dear Editor: Skin manifestations in systemic lupus erythematosus (SLE) are very heterogeneous. Recently, Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN)-like lupus erythematosus (LE) has been reported. Clinically, this condition presents with photodistributed exanthema and minimal mucositis. The onset of the rash is insidious with a prolonged clinical course1. A 16-year-old Korean woman presented with a 4-week history of gradually progressive development of painful, annular, erythematous, flattened, and blistering eruptions. Crusting presented on the face, V-neck area, upper back, and dorsum of the hands, and involved less than 10% of body surface area. The lips had erosions and crusts (Fig. 1). Eye and genital examinations were unremarkable. Previous medical history included malar rash and diffuse alopecia. No relevant medications had been newly administered. Fig. 1 Photodistributed erythematous flattened vesiculobullous eruptions with crusts on the face, V-neck area and the dorsum of hands and erosion on the lips. Skin biopsy from the back revealed a subepidermal blister with exocytosis and superficial perivascular infiltration of lymphocytes and neutrophils. Marked necrosis of keratinocytes of the suprabasal layer and interface dermatitis were manifested (Fig. 2). Direct immunofluorescence microscopy was remarkable in that linear deposits of immunoglobulin G, C3, and C1q were shown at the basement membrane zone. Fig. 2 Subepidermal blister with exocytosis and superficial perivascular infiltration of lymphocytes and neutrophils, marked necrosis of keratinocytes of the suprabasal layer and interface change (H&E, ×100). Laboratory investigations demonstrated anemia (hemoglobin 10.9 g/dl), leukopenia (3,600/mm3), and a normal platelet count. The antinuclear antibody titer was positive (1:640 homogeneous pattern), anti-double-stranded DNA was positive, anti-Ro/SS-A was positive and anti-La/SS-B was negative. Anti-Sm was positive, anti-nucleosome, anti-histones, and rheumatoid factor were negative. C3 and C4 levels were markedly low at 47.2 g/dl and 13.6 g/dl, respectively. Plasma creatinine was 0.65 mg/dl and the 24-hour urine proteinuria was 1,589 mg/day. Lupus nephritis class IIA was diagnosed from kidney biopsy. Liver function tests were unremarkable. Eventually, SJS-like cutaneous presentation with juvenile SLE was diagnosed based on the above findings. Treatment regimen included oral hydroxychloroquine 200 mg, deflazacort 48 mg per day with gradual tapering. Lesions improved after dressing on the denuded area and applying topical corticosteroid. Skin is the second most commonly affected organ system in SLE2. A bullous eruption in the setting of SLE can be a diagnostic challenge. Classic SJS/TEN, SJS/TEN-like LE, drug-induced cutaneous LE, bullous LE, Rowell's syndrome, and immunobullous diseases need to be considered in the differential diagnosis3. Indirect immunofluorescence is an effective method to diagnose bullous LE, but the present patient did not undergo this test. However, bullous LE appears with various-sized tense blisters, which is clinically different from the patient's presentation. Usually, SJS/TEN-like LE develops as a result of severe inflammatory epidermal basal layer damage. Vacuolar degeneration leads to subepidermal blistering and almost full-thickness epidermal necrosis1,4. SJS/TEN-like LE is often triggered by excessive ultraviolet exposure with an underlying predisposition to SLE. These patients often have anti-Ro antibody. Anti-Ro may be associated with increased risk of photosensitive rash4. The standard treatment of SJS/TEN-like LE remains controversial. Corticosteroids were prescribed in the present case because of continuing lupus activity. Chloroquine was combined for immunomodulation. In previous reports of TEN-like acute cutaneous LE, intravenous immunoglobulin, and plasmapheresis were successful5. To our knowledge, SJS-like skin lesions with juvenile SLE have rarely been reported in the literature. This was the first case reported in Korea.

A Case Of Autoimmune Hepatitis With Microadenoma Of Pituitary

Here, a case of autoimmune hepatitis in 34 yrs old lady has been described. She presented with prolonged jaundice, amenorrhea, arthritis and lactation. In laboratory examination, her aminotransferases, alkaline phosphatase and all immunoglobulins were raised. Her serum was positive for antinuclear antibody, anti SLA antibody and antibody to F-actin. Other autoantibodies like anti ds DNA, anti SSA, anti SSB, anti Scl 70, anti Jo-1, anti-centromere and anti-cardiolipinAb were negative. There were no clinical features of any other autoimmune disease. On MRI examination, microadenoma of pituitary gland was detected and her serum prolactin & T4 level were also high. She was finally diagnosed as a case of AIH with pituitary microadenomaand anti SLA Ab, which is an uncommon entity.She was kept on steroid and Bromocriptine, but follow up could not be done. This case suggests that AutoImmune Hepatitis (AIH) with ANA, F-actin and anti SLAAb may present with Prolactinoma.

Rare Case of Lupus Nephritis With Negative Antinuclear Antibodies, Double-Stranded DNA Antibodies and Positive Anti-Ro/SSA Antibodies

Systemic lupus erythematosus (SLE) is an autoimmune multisystem disease that is characterized by various antibodies to nuclear and cytoplasmic antigens and diagnosed by either fulfilling the 2012 Systemic Lupus International Collaborating Clinics (SLICC) criteria, American College of Rheumatology (ACR) criteria or by Renal Biopsy. Renal involvement is common in SLE and is primarily related to anti-double-stranded DNA antibodies. However, small group of SLE nephritis patients have shown negative anti-dsDNA and ANA. We present a case of 25-year-old female who presented with proteinuria and negative serum antibodies except anti-Ro/SSA. Renal biopsy was performed and was consistent with class IV lupus nephritis (LN). In this report, we highlight the possible role of anti-Ro antibodies in the pathogenesis and the prognosis of LN, although the mechanism is yet to be understood. Anti-Ro/SSA antibodies might play an important role in the pathogenesis and prognosis in LN. However, further studies are required to understand the exact mechanism. World J Nephrol Urol. 2016;5(2):48-49 doi: http://dx.doi.org/10.14740/wjnu272e

Association of anti-Ro52, anti-Ro60 and anti-La antibodies with diagnostic, clinical and laboratory features in a referral hospital in Jerez, Spain

ObjectiveSeveral antibodies have proven to be useful in autoimmune diseases, as markers for diagnosis, prognosis or clinical manifestations. Our objective was to evaluate the diagnosis and manifestations associated for antibodies anti-Ro52, anti-Ro60 and anti-La at a referral hospital in Spain. MethodsWe retrospectively analyzed the antigenic specificities of the consecutive samples submitted to the Immunology Unit for antinuclear antibody screening between 2002 and 2012. We included patients with more than one positive sample for some of the autoantibodies anti-Ro52, anti-Ro60 or anti-La. We also reviewed diagnosis, clinical and laboratory features. As dependent variable we evaluated possible combinations of anti-Ro52, anti-Ro60 and anti-La. Results322 patients, 91% females, were studied (age 44.3±15.51 years). The most frequent diagnosis was Sjögren's syndrome (40.06%) and systemic lupus erythematosus (SLE) (36.6%). The most prevalent pattern by indirect immunofluorescence was the fine speckled (69.9%). Anti-Ro52+/anti-Ro60+/anti-La+ combination was positively associated with fine speckled pattern (p: 0.001) and negatively with homogeneous (p: 0.016) and cytoplasmic pattern (p: 0.002). Isolated anti-Ro52+ was negatively associated with fine speckled pattern (p<0.001) and positively with the cytoplasmic one (p<0.001). The main positive associations with clinical symptoms were xerostomia and xerophthalmia with anti-Ro52+/anti-Ro60+/anti-La+ (p<0.001), oral ulcers with anti-Ro52+/anti-Ro60+/anti-La− (p: 0.002) and alopecia with anti-Ro52−/anti-Ro60+/anti-La− (p: 0.003). Negative associations were xerophthalmia and photosensitivity with anti-Ro52+/anti-Ro60−/anti-La− (p: 0.003). Laboratory positive associations were hypergammaglobulinemia with anti-Ro52+/anti-Ro60+/anti-La+ (p: 0.003), and hypocomplementemia with anti-Ro52−/anti-Ro60+/anti-La− (p: 0.003). Leucopenia was negatively associated with anti-Ro52+/anti-Ro60−/anti-La− (p: 0.003). ConclusionOur study found significant relationships between clinical and laboratory manifestations with different patterns of antibodies to anti-Ro52, anti-Ro60 and anti-La. The combination of antibodies might be clinically useful due to prognostic and therapeutic implications.

Morbidities in pregnancy associated with systemic lupus erythematous

The association between systemic lupus erythematosus (SLE) and pregnancy is not a rare event, but these pregnacy are associated with an increased risk of preeclampsia, fetal growth restriction, fetal stillbirth, prematurity and neonatal death. Nephritis is an important complication of SLE and a factor for maternal and fetal morbidity. Studies of the impact of SLE and pregnancy morbidities generate conflicting results. The aim of these study was to realize a systematic analysis in the literature concerning the pregnancy outcome in women with SLE and SLE associated with lupus nephritis. We searched the electronic database in literature and random effects of analytycal methods were used to evaluate pregnancy complications rates. Also the association between pregnancy and nephritis it is not very often encountered in different articles. Active SLE and the presence of antiphospholipid antibodies (APA) are considered the most powerful predictors of perinatal morbidity. We found that a significant number of pregnancies occur during periods of active nephritis (19%), and have positive APAs (26.2%). Up to 75% of patients with SLE have clinically evident renal disease. Lupus flare in pregnancy is one of the major issues associated with SLE. However, studies report variable flare rates in pregnancy between 25-65%. Other important perinatal complications associated with SLE in pregnancy are: gestational hypertension (16.3%), fetal growth restriction (12,7%), preeclampsia (7,6%), preterm delivery (39,4%), stillbirth (3,6%), neonatal death (2,5%). Neonatal lupus syndromes is a form of passively acquired fetal autoimmunity from maternal antibodies, anti-Ro and anti-La antibodies with important cardiac involvement, most commonly congenital heart block. Previous and actual lupus nephritis is associated with negative effects on preganancy and with a deterioration of renal function. Despite considerable improvement in success rates, suboptimal obstetrical outcomes still remain a cause for concern. Best pregnancy results can be obtained if appropriately managed by a multidisciplinary team of physicians.

The Prevalence of Thyroid Dysfunction in Patients With Systemic Lupus Erythematosus.

Background:Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease caused by immune system-mediated tissue damage. Autoimmune thyroiditis (AT) is an organ-specific disease associated with production of a variety of antibodies such as antinuclear antibodies, anti-double-stranded DNA, anti-Ro antibodies and anti-cardiolipin antibodies.Objectives:The aim of this study was to evaluate the prevalence of thyroid dysfunction and thyroid auto-antibodies in patients with SLE and its relation to SLE disease and other autoantibodies.Patients and Methods:This was a case-control study. The study included a total of 88 patients with SLE and 88 age- and sex-matched healthy volunteers as control group. Two study groups were compared regarding thyroid function test, antinuclear antibody (ANA), antibodies to double-stranded DNA (dsDNA), anti- thyroglobulin antibody (anti-Tg), and anti-thyroid peroxidase (anti-TPO) antibody.Results:The mean age of SLE patients and controls were 32.16 ± 9.19 and 32.48 ± 9.47 years, respectively (P = 0.821). Patients had significantly higher prevalence (43.2% vs. 23.9%; P = 0.015) and titers (221.8 ± 570.5 vs. 78.2 ± 277.2; P = 0.036) of antibodies to Tg compared to controls. The patients had significantly lower titers of T3 compared to controls (125.2 ± 35.6 vs. 136.2 ± 26.5; P = 0.021). The titers of T4, TSH and anti-TPO antibody did not differ significantly between the two study groups.Conclusions:Thyroid dysfunction was not higher in SLE patients compared to healthy individuals. However, anti-Tg antibodies were higher in SLE patients. It has not yet been established that thyroid function tests should be performed routinely in SLE patients.