Presence Of anti-SSA Antibodies Research Articles

Diagnostic value of minor salivary gland biopsy for Sjögren's syndrome in children: A monocentric retrospective study over 10 years

ObjectivesMinor salivary gland biopsy (MSGB) is a minimally invasive test used in suspected autoimmune diseases. Our study goal was to evaluate diagnostic performance of MSGB in children suspected of Sjögren's syndrome (SS). MethodsWe did a retrospective monocentric study on patients under 18years old who had a MSGB between October 2011 and December 2021 at Bicêtre University Hospital. Biopsy was considered positive if focus score was positive or Chisholm-Mason score was superior to 2. ResultsSixty-six MSGB were analysed in SS indication, 23/66 (35%) were positive and 13/23 (57%) were associated with a confirmed final diagnosis. MSGB was sensitive and specific (Se=81%, Sp=80), but with low positive and negative predictive value (57% and 7%). Twenty of 64 MSGB also had positive anti-SSA antibodies. Anti-SSA antibodies improved MSGB specificity (98%). ConclusionMSGB demonstrates good sensitivity and specificity, but the predictive values and likelihood ratios make it a poor screening test. However, when combined with other criteria such as the presence of anti-SSA antibodies, the specificity of MSGB is improved. A larger prospective study should be carried out to support our results and clarify the good indications for MSGB.

An immuno-lipidomic signature revealed by metabolomic and machine-learning approaches in labial salivary gland to diagnose primary Sjögren's syndrome.

Assessing labial salivary gland exocrinopathy is a cornerstone in primary Sjögren's syndrome. Currently this relies on the histopathologic diagnosis of focal lymphocytic sialadenitis and computing a focus score by counting lym=phocyte foci. However, those lesions represent advanced stages of primary Sjögren's syndrome, although earlier recognition of primary Sjögren's syndrome and its effective treatment could prevent irreversible damage to labial salivary gland. This study aimed at finding early biomarkers of primary Sjögren's syndrome in labial salivary gland combining metabolomics and machine-learning approaches. We used a standardized targeted metabolomic approach involving high performance liquid chromatography coupled with mass spectrometry among newly diagnosed primary Sjögren's syndrome (n=40) and non- primary Sjögren's syndrome sicca (n=40) participants in a prospective cohort. A metabolic signature predictive of primary Sjögren's syndrome status was explored using linear (logistic regression with elastic-net regularization) and non-linear (random forests) machine learning architectures, after splitting the data set into training, validation, and test sets. Among 126 metabolites accurately measured, we identified a discriminant signature composed of six metabolites with robust performances (ROC-AUC = 0.86) for predicting primary Sjögren's syndrome status. This signature included the well-known immune-metabolite kynurenine and five phospholipids (LysoPC C28:0; PCaa C26:0; PCaaC30:2; PCae C30:1, and PCaeC30:2). It was split into two main components: the first including the phospholipids was related to the intensity of lymphocytic infiltrates in salivary glands, while the second represented by kynurenine was independently associated with the presence of anti-SSA antibodies in participant serum. Our results reveal an immuno-lipidomic signature in labial salivary gland that accurately distinguishes early primary Sjögren's syndrome from other causes of sicca symptoms.

Neurological injury in primary Sjogren's syndrome.

Forty-eight patients with primary Sjogren's syndrome, attending outpatient clinics at Damascus Hospital between January 2020 and January 2022 in this cross-sectional study at the outpatient clinics, were interviewed and examined, and the necessary laboratory and radiological examinations were demanded. Information was collected on disease duration, onset time, and patterns of neurological symptoms. Forty-eight patients, including 42 females, aged 56.1±10.3 years were enroled.Central nervous system involvement was found in 34 patients. 85% of patients had generalized nerve manifestations, while local nerve manifestations were found in 77,5% of patients. The common neurological manifestation was headaches, then cognitive disorders, and the most common pattern of headache was migraine. Beck Depression Index showed a significant increase in the apathy evaluation scale.The study of cognitive changes showed a significant increase in the Mini-Mental State Examination (MMSE) index.Carotid Doppler showed the presence of injury in 42.4% of patients. The magnetic resonance imaging showed positive findings in 21 patients and positive evoked potentials in 52% of patients. Studies showing the prevalence of Sjogren's neurological injury patterns are insufficient, but this was changed when the criteria for diagnosing Sjogren's syndrome was modified, and the definition of neurological traits in the context of the syndrome was expanded.The presence of a high rate of headaches, cognitive changes, and fatigue confirms that generalized nervous system injuries are more common than local injuries. Migraine was the most common pattern of headache found in patients with the syndrome compared with other patterns such as tension headaches and headaches due to medications, especially analgesics.This was associated with the presence of anti-SSA antibodies and Raynaud's phenomenon, which suggest that the headache mechanism may be due to vascular endothelial dysfunction or an immune-mediated inflammation injury of the neurovascular system.The changes that appeared on the MRI images suggested premotor cortex involvement rather than mesolimbic cortical impairment, and its presence was also associated with SSA antibody positivity, and it is caused by inflammation. Primary Sjogren's syndrome should be considered as having any unspecified or specific neurological disorder.

Discriminative power of salivary gland ultrasound in relation to symptom-based endotypes in suspected and definite primary Sjögren's Syndrome

ObjectivesSalivary gland ultrasound (SGUS) is emerging as essential tool in primary Sjögren's Syndrome (pSS), but its link to symptom-based endotypes is unknown. Therefore, we explored SGUS outcomes in relation to endotypes in patients with definite and suspected pSS. MethodsDefinite pSS patients (n = 171) fulfilling the 2016 ACR/EULAR classification criteria, and suspected pSS patients (n = 119), positive for at least one criterion, were included in the Belgian Sjögren's Syndrome Transition Trial (BeSSTT). Stratification into endotypes according to the Newcastle Sjögren's Stratification Tool resulted in low symptom burden (LSB), pain dominant with fatigue (PDF), dryness dominant with fatigue (DDF) and high symptom burden (HSB). SGUS was assessed with Hocevar score (0-48). The dataset was randomly divided into a discovery (n = 203) and replication (n = 87) cohort. ResultsSGUS had strong discriminative power for pSS classification (AUC=0.74), especially in DDF (AUC=0.89). In definite pSS, Hocevar scores in DDF were high compared to other endotypes (38 (20-44) versus 18 (9-33); p < 0.001). Patients with highest SGUS-scores showed more sicca and laboratory abnormalities. Moreover, a subset of young, anti-SSA/Ro positive patients not fulfilling classification criteria showed clear SGUS abnormalities. Replication showed similar results. ConclusionsSGUS-scores were significantly higher in definite pSS with DDF endotype, providing the first evidence of imaging abnormalities in salivary glands matching distinct biological profiles ascribed to pSS endotypes. Additionally, a subset of patients with potential early disease was detected based on presence of anti-SSA antibodies and high SGUS-scores. These results underscore the role of SGUS as powerful tool both in pSS classification and stratification.

Effects of anti-SSA antibodies on the response to methotrexate in rheumatoid arthritis: A retrospective multicenter observational study.

Comparison of clinical response to methotrexate between anti-SSA antibody-positive and -negative patients with methotrexate-naïve rheumatoid arthritis and investigate the reasons for the differences in the response. For this multicenter retrospective cohort study, a total of 210 consecutive patients with rheumatoid arthritis who newly initiated methotrexate were recruited. The effects of anti-SSA antibody positivity on achieving a low disease activity according to the 28-joint Disease Activity Score based on C-reactive protein after 6 months of methotrexate administration were investigated using a logistic regression analysis. This study involved 32 and 178 anti-SSA antibody-positive and -negative patients, respectively. The rate of achieving low disease activity according to the 28-joint Disease Activity Score based on C-reactive protein at 6 months was significantly lower in the anti-SSA antibody-positive group than in the anti-SSA antibody-negative group (56.2% vs. 75.8%, P = 0.030). After 6 months, anti-SSA antibody-positive patients had significantly higher scores on the visual analogue scale (median [interquartile range]: 22 [15-41] vs. 19 [5-30], P = 0.038) and were frequently prescribed nonsteroidal anti-inflammatory drugs (37.5% vs. 18.0%, P = 0.018). In conclusion, the presence of anti-SSA antibodies might be a predictive factor for insufficient responses to treat-to-target strategy in rheumatoid arthritis. Residual pain might contribute to the reduced clinical response to methotrexate in anti-SSA antibody-positive patients with rheumatoid arthritis.

Salivary gland ultrasonography in patients with connective tissue diseases: a multi-centre observational study.

US of salivary glands (SGUS) is a non-invasive tool that allows for diagnosing primary SS (pSS) or secondary SS (sSS). However, little is known about the prevalence of US findings of SS in other CTDs. The aim of this multi-centre observational study was to evaluate, in CTD patients with or without SS, the prevalence of abnormal SGUS findings and the possible association of the findings with clinical or biological phenotypes. B-Mode SGUS was performed by one operator blinded to clinical data. Each SG was semi-quantitatively rated on a scale from 0 to 4 according to the Jousse-Joulin score; a score ≥2 was considered pathological. Data for 194 patients were analysed (pSS, n = 30; sSS, n = 39; other CTDs, n = 77; controls, n = 48). SGUS findings were abnormal in 80%, 67%, 25% and 2% of patients, respectively. Independent of the underlying disease, age and sex, abnormal SGUS findings were significantly associated with presence of anti-SSA antibodies (P < 0.001), pSS (P < 0.001) and sSS (P < 0.01). Among SS patients, abnormal SGUS findings were associated with the presence of hypergammaglobulinemia, anti-SSA antibodies, objective eye dryness and increased anti-nuclear antibody level, with no difference in EULAR SS Disease Activity Index. Abnormal SGUS findings were associated with anti-SSA antibody positivity independent of the underlying disease. In SS patients, abnormal findings were associated with immunologic features and mouth involvement. Among CTD patients, SGUS changes may be associated with a particular immune profile.

Clinical Features, Autoantibodies, and Outcome of Neonatal Lupus Erythematosus

Objectives: To explore the clinical features, autoantibodies, and outcome of neonatal lupus erythematosus (NLE). Methods: We retrospectively reviewed all NLE cases from January 2012 to May 2019 that occurred in our department. Results: Cutaneous, cardiac, hematologic, and hepatobiliary manifestations were found in 36.7%, 56.7%, 56.7%, and 30.0% of cases, respectively. The presence of anti-SSA antibodies was correlated with cardiac presentation (p = .026) and the presence of anti-SSB antibodies was associated with cutaneous lesions (p = .015). During the follow-up, one patient with a third-degree atrioventricular block died, and a third-degree AV block persists in a child without a pacemaker at 4-years of age. No other manifestations of NLE were observed after the age of 12 months. Conclusions: Anti-SSA and anti-SSB are associated with cardiac and cutaneous manifestations in NLE. Most children with NLE have excellent outcomes with symptom resolution by one year. Complete congenital heart block may persist.

Polymyositis associated with hypothyroidism or hyperthyroidism: two cases and review of the literature

Studies confirming a possible relationship of polymyositis within thyroid dysfunction, either hypothyroidism or hyperthyroidism, are hardly available. To define the association, identify clinical, laboratory, electromyographic, and pathologic features in polymyositis (PM) patients with hypothyroidism or hyperthyroidism, we conducted a MEDLINE and Chinese biomedicine database search to identify relevant literature published in the past 25years. Seventeen cases were included. All patients were female (10 hypothyroidism patients, seven hyperthyroidism patients). The mean (SD) age of PM, hypothyroidism, and hyperthyroidism at diagnosis was 54.8 (16.7), 55.5 (16.5), and 32.7years (10.2), respectively. PM diagnosis can precede or parallel hypothyroidism while PM may occur following the diagnosis of hyperthyroidism. The most common comorbidities were malignant tumors in these disorders, including thymoma, colon cancer, and thyroid cancer. Muscle weakness was described in 100% of patients. Other common manifestations included muscles' atrophy and pain, deep tendon reflexes, polyarthralgia, and dysphagia. Most patients had markedly elevated creatine kinase and the presence of anti-Sjogren's syndrome A (SSA) antibodies was also found in two cases. Malignancy associated with PM may more frequently occur in hypothyroidism than in hyperthyroidism. The abnormalities on electromyography and biopsy did not differ from those findings of PM. Therapy consisting of corticosteroids, thyroid hormone, or anti-thyroid drugs was administrated; however, poor prognosis seemed to be associated with malignant tumors as well as older age and the presence of anti-SSA antibodies. It is reasonable to suggest that those patients should be routinely evaluated for thyroid function, especially in older female and patients suffering from cancers.

Systemic lupus erythematosus and pregnancy

This article critically analyses the data in the literature on pregnancy in women with systemic lupus erythematosus. Based on the results of recent controlled prospective studies, it is apparent that the long-standing opinion that pregnancy induces exacerbation of the disease should be revised. The presence of active disease and/or a significant loss of renal function at conception are not only associated with a high risk of maternal complications, but also with high frequencies of loss of the fetus, as well as pre- and dysmaturity. Recently, the presence of antiphospholipid antibodies, notably the lupus anticoagulant and anticardiolipin antibodies, has been recognized as being important for the occurrence of death of the fetus, in particular, late in the pregnancy. This is probably due to thrombosis occurring in the placental vessels. However, the results of randomized studies on treatment with antithrombotic drugs and/or procedures lowering, antibody levels must be available before we will know whether the presence of these antibodies should be coupled to specific instructions or not. Although there is a strong association between the neonatal lupus syndrome and the presence of anti-SSA antibodies in maternal blood, the finding of anti-SSA antibodies has up to now had no therapeutic implications. It is concluded that pregnancy in SLE deserves extensive preconceptional counseling and close cooperation between the internist, rheumatologist, obstetrician and the neonatologist.

Leukopenia in Still's Disease-Reply

In Reply.— We appreciate the comments of Drs Calmes and Bartholomew. Systemic lupus erythematosus was considered, but, the clinical picture of the two patients, along with the absence of serological abnormalities, excluded this diagnosis. We are familiar with the entity of ANA-negative SLE and its strong association with anti-SSA (or Ro) antibodies.1,2Serum samples from both patients were tested for specific ANA, including anti-SSA, and were found to be negative on multiple occasions. Nevertheless, the presence of anti-SSA antibodies is not restricted to SLE. In a recent study, these antibodies were demonstrated in the serum of patients with a variety of connective-tissue diseases, including two patients with otherwise typical Still's disease (one adult and one child).3 The dermatologic manifestations of Still's disease are very different from those of subacute cutaneous lupus. As in the two cases presented, the rashes of Still's disease are transient and nonphotosensitive, while those