A Global Systematic Literature Review of Ecosystem Services in Reef Environments.

Ecosystem services (ES) embrace contributions of nature to human livelihood and well-being. Reef environments provide a range of ES with direct and indirect contributions to people. However, the health of reef environments is declining globally due to local and large-scale threats, affecting ES delivery in different ways. Mapping scientific knowledge and identifying research gaps on reefs' ES is critical to guide their management and conservation. We conducted a systematic assessment of peer-reviewed articles published between 2007 and 2022 to build an overview of ES research on reef environments. We analyzed the geographical distribution, reef types, approaches used to assess ES, and the potential drivers of change in ES delivery reported across these studies. Based on 115 articles, our results revealed that coral and oyster reefs are the most studied reef ecosystems. Cultural ES (e.g., subcategories recreation and tourism) was the most studied ES in high-income countries, while regulating and maintenance ES (e.g., subcategory life cycle maintenance) prevailed in low and middle-income countries. Research efforts on reef ES are biased toward the Global North, mainly North America and Oceania. Studies predominantly used observational approaches to assess ES, with a marked increase in the number of studies using statistical modeling during 2021 and 2022. The scale of studies was mostly local and regional, and the studies addressed mainly one or two subcategories of reefs' ES. Overexploitation, reef degradation, and pollution were the most commonly cited drivers affecting the delivery of provisioning, regulating and maintenance, and cultural ES. With increasing threats to reef environments, the growing demand for assessing the contributions to humans provided by reefs will benefit the projections on how these ES will be impacted by anthropogenic pressures. The incorporation of multiple and synergistic ecosystem mechanisms is paramount to providing a comprehensive ES assessment, and improving the understanding of functions, services, and benefits.

Turbidity shapes shallow Southwestern Atlantic benthic reef communities.

Southwestern Atlantic reefs (Brazilian Province) occur along a broad latitudinal range (∼5°N-27°S) and under varied environmental conditions. We combined large-scale benthic cover and environmental data into uni- and multivariate regression tree analyses to identify unique shallow (<30 m) benthic reef communities and their environmental drivers along the Brazilian Province. Turbidity was the leading environmental driver of benthic reef communities, with the occurrence of two main groups: clear-water (dominated by fleshy macroalgae) and turbid (dominated by turf algae). Seven out of 14 scleractinian coral species were more abundant in the turbid group, thus corroborating the photophobic nature of some Brazilian corals. The most abundant scleractinian in Brazil (Montastraea cavernosa), largely dominated (71-93% of total coral cover) both, the shallow turbid and deeper clear-water reefs. Because these habitat types are widely recognized as potential climate refuges, local threats (e.g. pollution, overfishing) should be averted.

A tool for a race against time: Dispersal simulations to support ongoing monitoring program of the invasive coral Tubastraea coccinea.

Preventing, detecting, and monitoring invasive marine species is a big challenge as it is not possible to visualize all invasion extensions. Their early detection may be the best chance to achieve eradication. The Indo-pacific scleractinian coral Tubastraea coccinea invasion in the Atlantic dates from the late 1930s. Since then, disruptive populations were found along ~8.000 km of west Atlantic, and in the Canarian Islands of Spain (east Atlantic), related to vessel fouling in the oil and gas industry. Their impacts have been noticed from endemic species to ecosystems. In Brazil, initiatives to control Tubastraea spp. have been done mostly by local environmental managers and researchers, but recently a National Plan for Prevention, Control and Monitoring (NPPCM) for Tubastraea spp. was approved. We applied an Individual-based Model within the invasion history of Tubastraea coccinea in its southern distribution limit in the Atlantic, on the rocky shore of the Arvoredo Biological Marine Reserve. We indicated hotspots for the occurrence of possible emerging invasion sites in the region and expect to support ongoing monitoring programs in defining priority areas for their early detection. The model is easily replicated and might be a valuable tool for decision makers.

Large-scale patterns of benthic marine communities in the Brazilian Province.

As marine ecosystems are influenced by global and regional processes, standardized information on community structure has become crucial for assessing broad-scale responses to natural and anthropogenic disturbances. Extensive biogeographic provinces, such as the Brazilian Province in the southwest Atlantic, present numerous theoretical and methodological challenges for understanding community patterns on a macroecological scale. In particular, the Brazilian Province is composed of a complex system of heterogeneous reefs and a few offshore islands, with contrasting histories and geophysical-chemical environments. Despite the large extent of the Brazilian Province (almost 8,000 kilometers), most studies of shallow benthic communities are qualitative surveys and/or have been geographically restricted. We quantified community structure of shallow reef habitats from 0° to 27°S latitude using a standard photographic quadrat technique. Percent cover data indicated that benthic communities of Brazilian reefs were dominated by algal turfs and frondose macroalgae, with low percent cover of reef-building corals. Community composition differed significantly among localities, mostly because of their macroalgal abundance, despite reef type or geographic region, with no evident latitudinal pattern. Benthic diversity was lower in the tropics, contrary to the general latitudinal diversity gradient pattern. Richness peaked at mid-latitudes, between 20°S to 23°S, where it was ~3.5-fold higher than localities with the lowest richness. This study provides the first large-scale description of benthic communities along the southwestern Atlantic, providing a baseline for macroecological comparisons and evaluation of future impacts. Moreover, the new understanding of richness distribution along Brazilian reefs will contribute to conservation planning efforts, such as management strategies and the spatial prioritization for the creation of new marine protected areas.

Minor salivary gland fibrosis in Sjögren's syndrome is elevated, associated with focus score and not solely a consequence of aging.

OBJECTIVES: Evaluate the presence of minor salivary gland (SG) fibrosis in primary Sjögren's syndrome (pSS) as a function of disease pathology or a consequence of ageing. METHODS: Subjects with sicca symptoms attending a Sjögren's research clinic were classified by American European Consensus Group (AECG) criteria as either pSS or non-SS (nSS). Discovery (n=34 pSS, n=28 nSS) and replication (n=35 pSS, n=31 nSS) datasets were evaluated. Minor SG cross-sections from haematoxylin and eosin stained slides were imaged, digitally reconstructed and analysed for percent area fibrosis. Relationships between SG fibrosis, age, and clinical measures were evaluated using Spearman correlations. Association with SS was assessed by: ROC curve, Variable Selection Using Random Forests (VSURF) and uni- and bi-variate regression analyses. RESULTS: SS subjects had significantly more fibrotic tissue in their minor labial salivary glands (median 24.39%, range 5.12-51.67%) than nSS participants (median 16.7%, range 5.97-38.65%, p<0.0001); age did not differ between groups (average ± SD pSS 50.2 ±13.9 years, nSS 53.8±12.4 years). In both the discovery and replication data sets, multiple regression models showed that the area of minor salivary gland fibrosis predicted pSS significantly better than age alone. Age-corrected linear regression revealed that the area of minor salivary gland fibrosis positively associated with vanBijsterveld score (p=0.042) and biopsy focus score (p=0.002). ROC curve and VSURF analyses ranked fibrosis as a significantly more important variable for subject discrimination than age. CONCLUSIONS: SG fibrosis is an element of pSS pathology that is related to focus score and is not solely attributable to age.

Fatty infiltration of the minor salivary glands is a selective feature of aging but not Sjögren's syndrome.

OBJECTIVE: Determine the presence and assess the extent of fatty infiltration of the minor salivary glands (SG) of primary SS patients (pSS) as compared to those with non-SS sicca (nSS). METHODS: Minor SG biopsy samples from 134 subjects with pSS (n = 72) or nSS (n = 62) were imaged. Total area and fatty replacement area for each glandular cross-section (n = 4-6 cross-sections per subject) were measured using Image J (National Institutes of Health, Bethesda, MD). The observer was blinded to subject classification status. The average area of fatty infiltration calculated per subject was evaluated by logistic regression and general linearized models (GLM) to assess relationships between fatty infiltration and clinical exam results, extent of fibrosis and age. RESULTS: The average area of fatty infiltration for subjects with pSS (median% (range) 4.97 (0.05-30.2)) was not significantly different from that of those with nSS (3.75 (0.087-41.9). Infiltration severity varied widely, and subjects with fatty replacement greater than 6% were equivalently distributed between pSS and nSS participants (χ2 p = .50). Age accounted for all apparent relationships between fatty infiltration and fibrosis or reduced saliva flow. The all-inclusive GLM for prediction of pSS versus non-SS classification including fibrosis, age, fatty replacement, and focus score was not significantly different from any desaturated model. In no iteration of the model did fatty replacement exert a significant effect on the capacity to predict pSS classification. CONCLUSIONS: Fatty infiltration is an age-associated phenomenon and not a selective feature of Sjögren's syndrome. Sicca patients who do not fulfil pSS criteria have similar rates of fatty infiltration of the minor SG.

Rare X Chromosome Abnormalities in Systemic Lupus Erythematosus and Sjögren's Syndrome.

OBJECTIVE: Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE) are related by clinical and serologic manifestations as well as genetic risks. Both diseases are more commonly found in women than in men, at a ratio of ~10 to 1. Common X chromosome aneuploidies, 47,XXY and 47,XXX, are enriched among men and women, respectively, in either disease, suggesting a dose effect on the X chromosome. METHODS: We examined cohorts of SS and SLE patients by constructing intensity plots of X chromosome single-nucleotide polymorphism alleles, along with determining the karyotype of selected patients. RESULTS: Among ~2,500 women with SLE, we found 3 patients with a triple mosaic, consisting of 45,X/46,XX/47,XXX. Among ~2,100 women with SS, 1 patient had 45,X/46,XX/47,XXX, with a triplication of the distal p arm of the X chromosome in the 47,XXX cells. Neither the triple mosaic nor the partial triplication was found among the controls. In another SS cohort, we found a mother/daughter pair with partial triplication of this same region of the X chromosome. The triple mosaic occurs in ~1 in 25,000-50,000 live female births, while partial triplications are even rarer. CONCLUSION: Very rare X chromosome abnormalities are present among patients with either SS or SLE and may inform the location of a gene(s) that mediates an X dose effect, as well as critical cell types in which such an effect is operative.

Identification of a Sjögren's syndrome susceptibility locus at OAS1 that influences isoform switching, protein expression, and responsiveness to type I interferons.

Sjögren's syndrome (SS) is a common, autoimmune exocrinopathy distinguished by keratoconjunctivitis sicca and xerostomia. Patients frequently develop serious complications including lymphoma, pulmonary dysfunction, neuropathy, vasculitis, and debilitating fatigue. Dysregulation of type I interferon (IFN) pathway is a prominent feature of SS and is correlated with increased autoantibody titers and disease severity. To identify genetic determinants of IFN pathway dysregulation in SS, we performed cis-expression quantitative trait locus (eQTL) analyses focusing on differentially expressed type I IFN-inducible transcripts identified through a transcriptome profiling study. Multiple cis-eQTLs were associated with transcript levels of 2'-5'-oligoadenylate synthetase 1 (OAS1) peaking at rs10774671 (PeQTL = 6.05 × 10-14). Association of rs10774671 with SS susceptibility was identified and confirmed through meta-analysis of two independent cohorts (Pmeta = 2.59 × 10-9; odds ratio = 0.75; 95% confidence interval = 0.66-0.86). The risk allele of rs10774671 shifts splicing of OAS1 from production of the p46 isoform to multiple alternative transcripts, including p42, p48, and p44. We found that the isoforms were differentially expressed within each genotype in controls and patients with and without autoantibodies. Furthermore, our results showed that the three alternatively spliced isoforms lacked translational response to type I IFN stimulation. The p48 and p44 isoforms also had impaired protein expression governed by the 3' end of the transcripts. The SS risk allele of rs10774671 has been shown by others to be associated with reduced OAS1 enzymatic activity and ability to clear viral infections, as well as reduced responsiveness to IFN treatment. Our results establish OAS1 as a risk locus for SS and support a potential role for defective viral clearance due to altered IFN response as a genetic pathophysiological basis of this complex autoimmune disease.

Effect of Tobacco Smoking on The Clinical, Histopathological, and Serological Manifestations of Sjögren's Syndrome.

OBJECTIVES: To assess the association of smoking habits with the clinical, serological, and histopathological manifestations of Sjögren's syndrome (SS) and non-Sjögren's sicca (non-SS sicca). METHODS: Cross-sectional case-control study of 1288 patients with sicca symptoms (587 SS and 701 non-SS sicca) evaluated in a multi-disciplinary research clinic. Smoking patterns were obtained from questionnaire data and disease-related clinical and laboratory data were compared between current, past, ever, and never smokers. RESULTS: Current smoking rates were 4.6% for SS patients compared to 14.1% in non-SS sicca (p = 5.17x10E-09), 18% in a local lupus cohort (p = 1.13x10E-14) and 16.8% in the community (p = 4.12x10E-15). Current smoking was protective against SS classification (OR 0.35, 95%CI 0.22-0.56, FDR q = 1.9E10-05), focal lymphocytic sialadenitis (OR 0.26, 95%CI 0.15-0.44, FDR q = 1.52x10E-06), focus score ≥1 (OR 0.22, 95%CI 0.13-0.39, FDR q = 1.43x10E-07), and anti-Ro/SSA(+) (OR 0.36, 95%CI 0.2-0.64, FDR q = 0.0009); ever smoking was protective against the same features and against anti-La/SSB(+) (OR 0.52, 95%CI 0.39-0.70, FDR q = 5.82x10E-05). Duration of smoking was inversely correlated with SS even after controlling for socioeconomic status, BMI, alcohol and caffeine consumption. CONCLUSIONS: Current tobacco smoking is negatively and independently associated with SS, protecting against disease-associated humoral and cellular autoimmunity. The overall smoking rate amongst SS patients is significantly lower than in matched populations and the effects of smoking are proportional to exposure duration. In spite of the protective effects of tobacco on SS manifestations, it is associated with other serious comorbidities such as lung disease, cardiovascular risk and malignancy, and should thus be strongly discouraged in patients with sicca.

Klinefelter's syndrome (47,XXY) is in excess among men with Sjögren's syndrome.

Primary Sjögren's syndrome (pSS) has a strong female bias. We evaluated an X chromosome dose effect by analyzing 47,XXY (Klinefelter's syndrome, 1 in 500 live male births) among subjects with pSS. 47,XXY was determined by examination of fluorescence intensity of single nucleotide polymorphisms from the X and Y chromosomes. Among 136 pSS men there were 4 with 47,XXY. This was significantly different from healthy controls (1 of 1254 had 47,XXY, p=0.0012 by Fisher's exact test) as well men with rheumatoid arthritis (0 of 363 with 47,XXY), but not different compared to men with systemic lupus erythematosus (SLE) (4 of 136 versus 8 of 306, Fisher's exact test p=NS). These results are consistent with the hypothesis that the number of X chromosomes is critical for the female bias of pSS, a property that may be shared with SLE but not RA.

Previous diagnosis of Sjögren's Syndrome as rheumatoid arthritis or systemic lupus erythematosus.

OBJECTIVE: The diagnosis of SS is often difficult and many patients are symptomatic for years with other diagnoses before confirmation of SS. Our aim was to determine whether overlapping clinical and serologic features with RA and SLE may in part drive the misdiagnoses. METHODS: A total of 1175 sicca patients were evaluated in a multidisciplinary clinic and classified as having SS based on the American-European Consensus Group Criteria. They were interrogated for a past history of suspicion or diagnosis of RA, SLE or SSc. These diseases were confirmed or ruled out by applying the corresponding classification criteria if the patients responded affirmatively. RESULTS: Of these, 524 (44.6%) subjects reported previous diagnosis or suspicion of RA, SLE or SSc, which was confirmed in 130 (24.8%) but excluded in 394 (75.2%) subjects. Of those previously diagnosed with another illness, 183 (34.9%) met the criteria for primary SS. RF was present in 70/191 patients with previous diagnosis of RA compared with 445/845 without a prior RA diagnosis (P = 3.38E-05), while 128/146 with a diagnosis of SLE had positive ANA compared with 622/881 without the diagnosis (P = 8.77E-06). Age also influenced former diagnoses: people with suspected RA were older than those without the diagnosis (P = 5.89E-06), while patients with SLE suspicion were younger (P = 0.0003). Interestingly, the previous diagnoses did not significantly delay a final classification of SS. CONCLUSION: Among subjects classified as SS, the presence of a positive ANA or RF was associated with a previous, apparently erroneous diagnosis of SLE or RA, respectively.

Genetic susceptibility loci of idiopathic interstitial pneumonia do not represent risk for systemic sclerosis: a case control study in Caucasian patients.

BACKGROUND: Systemic sclerosis (SSc)-related interstitial lung disease (ILD) has phenotypic similarities to lung involvement in idiopathic interstitial pneumonia (IIP). We aimed to assess whether genetic susceptibility loci recently identified in the large IIP genome-wide association studies (GWASs) were also risk loci for SSc overall or severity of ILD in SSc. METHODS: A total of 2571 SSc patients and 4500 healthy controls were investigated from the US discovery GWAS and additional US replication cohorts. Thirteen IIP-related selected single nucleotide polymorphisms (SNPs) were genotyped and analyzed for their association with SSc. RESULTS: We found an association of SSc with the SNP rs6793295 in the LRRC34 gene (OR = 1.14, CI 95 % 1.03 to 1.25, p value = 0.009) and rs11191865 in the OBFC1 gene (OR = 1.09, CI 95 % 1.00 to 1.19, p value = 0.043) in the discovery cohort. Additionally, rs7934606 in MUC2 (OR = 1.24, CI 95 % 1.01 to 1.52, p value = 0.037) was associated with SSc-ILD defined by imaging. However, these associations failed to replicate in the validation cohort. Furthermore, SNPs rs2076295 in DSP (ß = -2.29, CI 95 % -3.85 to -0.74, p value = 0.004) rs17690703 in SPPL2C (ß = 2.04, CI 95 % 0.21 to 3.88, p value = 0.029) and rs1981997 in MAPT (ß = 2.26, CI 95 % 0.35 to 4.17, p value = 0.02) were associated with percent predicted forced vital capacity (FVC%) even after adjusting for the anti-topoisomerase (ATA)-positive subset. However, these associations also did not replicate in the validation cohort. CONCLUSIONS: Our results add new evidence that SSc and SSc-related ILD are genetically distinct from IIP, although they share phenotypic similarities.

X Chromosome Dose and Sex Bias in Autoimmune Diseases: Increased Prevalence of 47,XXX in Systemic Lupus Erythematosus and Sjögren's Syndrome.

OBJECTIVE: More than 80% of autoimmune disease predominantly affects females, but the mechanism for this female bias is poorly understood. We suspected that an X chromosome dose effect accounts for this, and we undertook this study to test our hypothesis that trisomy X (47,XXX; occurring in ∼1 in 1,000 live female births) would be increased in patients with female-predominant diseases (systemic lupus erythematosus [SLE], primary Sjögren's syndrome [SS], primary biliary cirrhosis, and rheumatoid arthritis [RA]) compared to patients with diseases without female predominance (sarcoidosis) and compared to controls. METHODS: All subjects in this study were female. We identified subjects with 47,XXX using aggregate data from single-nucleotide polymorphism arrays, and, when possible, we confirmed the presence of 47,XXX using fluorescence in situ hybridization or quantitative polymerase chain reaction. RESULTS: We found 47,XXX in 7 of 2,826 SLE patients and in 3 of 1,033 SS patients, but in only 2 of 7,074 controls (odds ratio in the SLE and primary SS groups 8.78 [95% confidence interval 1.67-86.79], P = 0.003 and odds ratio 10.29 [95% confidence interval 1.18-123.47], P = 0.02, respectively). One in 404 women with SLE and 1 in 344 women with SS had 47,XXX. There was an excess of 47,XXX among SLE and SS patients. CONCLUSION: The estimated prevalence of SLE and SS in women with 47,XXX was ∼2.5 and ∼2.9 times higher, respectively, than that in women with 46,XX and ∼25 and ∼41 times higher, respectively, than that in men with 46,XY. No statistically significant increase of 47,XXX was observed in other female-biased diseases (primary biliary cirrhosis or RA), supporting the idea of multiple pathways to sex bias in autoimmunity.

Antinuclear antibody-negative systemic sclerosis.

OBJECTIVE: To examine the demographic and clinical characteristics of systemic sclerosis (SSc) patients without antinuclear antibodies (ANA) compared to ANA-positive patients. METHODS: SSc patients enrolled in the Scleroderma Family Registry and DNA Repository were included. Relevant demographic and clinical data were entered by participating sites or obtained by chart review. ANA and SSc-related antibodies were determined in all investigated patients using commercially available kits at our laboratories. RESULTS: This study included 3249 patients, of whom 208 (6.4%) were ANA negative. The proportion of male patients was higher in the ANA-negative group (OR = 1.65; p = 0.008). ANA-negative patients experienced less vasculopathic manifestations of SSc. The percent predicted diffusing capacity of carbon monoxide (DLCO) was higher in ANA-negative patients (p = 0.03). Pulmonary arterial hypertension (PAH) per right heart catheterization was less common in the ANA-negative group (OR = 0.28; p = 0.03). Furthermore, patients with negative ANA had a lower prevalence of telangiectasias and digital ulcers/pits (OR = 0.59, p = 0.03 and OR = 0.38, p = 0.01, respectively). Although diffuse cutaneous involvement was more common, the modified Rodnan Skin Score (mRSS) was lower in the ANA-negative group (2.4 points lower, p = 0.05). Furthermore, they experienced more malabsorption (p = 0.05). There was no difference in the frequency of pulmonary fibrosis or scleroderma renal crisis. All-cause mortality was not different between the 2 groups (p = 0.28). CONCLUSIONS: In conclusion, the results of this study suggest that SSc patients who are ANA negative constitute a distinct subset of SSc with less vasculopathy (less PAH, digital ulcers, and fewer telangiectasias), a greater proportion of males, and possibly, more frequent lower gastrointestinal involvement.

Work disability, lost productivity and associated risk factors in patients diagnosed with systemic lupus erythematosus.

OBJECTIVE: To assess prevalence and correlates of work presenteeism, absenteeism and work disability (WD) in patients with systemic lupus erythematous (SLE) and matched controls. METHODS: Patients with SLE from six medical centres were recruited to complete a questionnaire consisting of several prevalidated survey instruments. The subject's rheumatologist completed medical history. Subjects recruited two non-SLE 'best friend' controls with matching demographics to complete a control survey. Analyses employed Student's t tests, χ(2) tests and logistic regression models. RESULTS: 344 subjects with SLE and 322 controls submitted completed questionnaires. Mean pain, fatigue, Brief Cognitive Symptoms Index (BCSI) scores and depressive symptoms were worse in patients with SLE with WD (all p<0.01). WD was associated with African-American race, older age (51-65 years) and less than 4-year college education (all p<0.01). High presenteeism was associated with low pain and fatigue levels, higher BCSI scores and negatively correlated with depressive symptoms (all p<0.05). Increased pain and fatigue were associated with elevated absenteeism (p<0.05). Subjects with physically and cognitively demanding work reported worse presenteeism compared with controls with similar jobs (77% vs 85%, p<0.05 and 75% vs 85%, p<0.001), respectively. Patients with most cognitively demanding jobs reported greater weekly absenteeism (mean, 5.9 h) compared with controls (mean, 6.9 overtime hours, p<0.05). CONCLUSIONS: The questionnaire demonstrated increased WD in SLE. Highly physical and highly cognitive jobs are challenging to patients with SLE and had increased absenteeism compared with controls. Depressive symptoms were correlated with better presenteeism without major socio-demographic determinants. Employability may be enhanced by improving treatment of depressive symptoms in patients with SLE.

The IRF5-TNPO3 association with systemic lupus erythematosus has two components that other autoimmune disorders variably share.

Exploiting genotyping, DNA sequencing, imputation and trans-ancestral mapping, we used Bayesian and frequentist approaches to model the IRF5-TNPO3 locus association, now implicated in two immunotherapies and seven autoimmune diseases. Specifically, in systemic lupus erythematosus (SLE), we resolved separate associations in the IRF5 promoter (all ancestries) and with an extended European haplotype. We captured 3230 IRF5-TNPO3 high-quality, common variants across 5 ethnicities in 8395 SLE cases and 7367 controls. The genetic effect from the IRF5 promoter can be explained by any one of four variants in 5.7 kb (P-valuemeta = 6 × 10(-49); OR = 1.38-1.97). The second genetic effect spanned an 85.5-kb, 24-variant haplotype that included the genes IRF5 and TNPO3 (P-valuesEU = 10(-27)-10(-32), OR = 1.7-1.81). Many variants at the IRF5 locus with previously assigned biological function are not members of either final credible set of potential causal variants identified herein. In addition to the known biologically functional variants, we demonstrated that the risk allele of rs4728142, a variant in the promoter among the lowest frequentist probability and highest Bayesian posterior probability, was correlated with IRF5 expression and differentially binds the transcription factor ZBTB3. Our analytical strategy provides a novel framework for future studies aimed at dissecting etiological genetic effects. Finally, both SLE elements of the statistical model appear to operate in Sjögren's syndrome and systemic sclerosis whereas only the IRF5-TNPO3 gene-spanning haplotype is associated with primary biliary cirrhosis, demonstrating the nuance of similarity and difference in autoimmune disease risk mechanisms at IRF5-TNPO3.

Validation of the brief cognitive symptoms index in Sjögren syndrome.

OBJECTIVE: The Brief Cognitive Symptoms Inventory (BCSI) is a short, self-report scale designed to measure cognitive symptomatology in patients with rheumatic disease. To facilitate research and clinical practice, we tested the internal consistency and validity of the BCSI in patients with Sjögren syndrome (SS). METHODS: Patients who met the American-European Consensus Group criteria for SS and healthy controls completed a questionnaire assessing symptoms including cognitive complaints. We calculated Cronbach's alpha to assess internal consistency and Pearson correlation coefficients to test for association between BCSI, symptoms, and demographic variables. Total score distribution was analyzed to establish cutoff criteria for differentiation of case versus non-case. We compared neuropsychological outcomes of patients with SS above and below the threshold BCSI score to assess the association of cognitive symptoms with objective cognitive deficits. RESULTS: Complete data were available on 144 patients with SS and 35 controls. Internal consistency of the BCSI was good. Scores were similar in all patient groups and patients reported more cognitive symptoms than controls (p < 0.0001). BCSI scores correlated moderately with pain, depression, anxiety, fatigue, and health quality. High scores for cognitive dysfunction were reported by 20% of the patients with SS and only 3% of controls. Patients with cognitive scores > 50 had more depression, fatigue, pain (effect size all > 1), and worse performance on multiple cognitive domains. CONCLUSION: The BCSI should be a useful tool for the study of cognitive symptoms in SS. Both self-report and standardized tests should be considered in screening for cognitive disorders in SS.

Comparison of the American-European Consensus Group Sjogren's syndrome classification criteria to newly proposed American College of Rheumatology criteria in a large, carefully characterised sicca cohort.

OBJECTIVE: To compare the performance of the American-European Consensus Group (AECG) and the newly proposed American College of Rheumatology (ACR) classification criteria for Sjögren's Syndrome (SS) in a well-characterised sicca cohort, given ongoing efforts to resolve discrepancies and weaknesses in the systems. METHODS: In a multidisciplinary clinic for the evaluation of sicca, we assessed features of salivary and lacrimal gland dysfunction and autoimmunity as defined by tests of both AECG and ACR criteria in 646 participants. Global gene expression profiles were compared in a subset of 180 participants. RESULTS: Application of the AECG and ACR criteria resulted in classification of 279 and 268 participants with SS, respectively. Both criteria were met by 244 participants (81%). In 26 of the 35 AECG+/ACR participants, the minor salivary gland biopsy focal score was ≥1 (74%), while nine had positive anti-Ro/La (26%). There were 24 AECG-/ACR+ who met ACR criteria mainly due to differences in the scoring of corneal staining. All patients with SS, regardless of classification, had similar gene expression profiles, which were distinct from the healthy controls. CONCLUSIONS: The two sets of classification criteria yield concordant results in the majority of cases and gene expression profiling suggests that patients meeting either set of criteria are more similar to other SS participants than to healthy controls. Thus, there is no clear evidence for increased value of the new ACR criteria over the old AECG criteria from the clinical or biological perspective. It is our contention, supported by this report, that improvements in diagnostic acumen will require a more fundamental understanding of the pathogenic mechanisms than is at present available.

Pain severity and neuropathic pain symptoms in primary Sjögren's syndrome: a comparison study of seropositive and seronegative Sjögren's syndrome patients.

OBJECTIVE: To compare clinical characteristics and patient-reported outcomes in seropositive versus seronegative primary Sjögren's syndrome (SS) patients and to investigate the effect of serologic status on the prevalence of chronic pain, comorbidity, and health quality. METHODS: Pain severity and neuropathic pain symptoms, comorbidity, and health status were assessed in 108 primary SS patients. Differences between patient groups were assessed by t-test and chi-square test, as well as adjusted pain-affect associations. The effect of predictor variables on pain severity was examined with multivariate regression. RESULTS: Pain severity was greater (P = 0.003) and physical function (P = 0.023) was reduced in the seronegative patients. Prevalence of neuropathic pain, depression, anxiety, and disability was similar between groups. Chronic pain, defined as daily pain for >3 months, was reported by 65% of seropositive (n = 65) and 75% of seronegative (n = 40) patients. After adjustment for age, sleep quality, and psychological distress, the difference in pain severity between seropositive and seronegative patients remained significant. CONCLUSION: Chronic pain is pervasive in both seropositive and seronegative primary SS patients, while pain severity and functional impairment are greater in seronegative patients. Neuropathic pain is equally prevalent and is the predominant pain phenotype in patients with moderate to severe pain. Accurate assessment of pain phenotypes is needed for more effective management of chronic pain in primary SS. The focus of future research should be to standardize assessment of pain and to identify the factors contributing to more severe pain in seronegative patients.