Among all the body fluids, breast milk is one of the richest sources of microRNAs (miRNAs). MiRNAs packaged within the milk exosomes are bioavailable to breastfeeding infants. The role of miRNAs in determining infant growth and the impact of maternal overweight/obesity on human milk (HM) miRNAs is poorly understood. The objectives of this study were to examine the impact of maternal overweight/obesity on select miRNAs (miR-148a, miR-30b, miR-29a, miR-29b, miR-let-7a and miR-32) involved in adipogenesis and glucose metabolism and to examine the relationship of these miRNAs with measures of infant body composition in the first 6 months of life. Milk samples were collected from a cohort of 60 mothers (30 normal-weight [NW] and 30 overweight [OW]/obese [OB]) at 1-month and a subset of 48 of these at 3 months of lactation. Relative abundance of miRNA was determined using real-time PCR. The associations between the miRNAs of interest and infant weight and body composition at one, three, and six months were examined after adjusting for infant gestational age, birth weight, and sex. The abundance of miR-148a and miR-30b was lower by 30% and 42%, respectively, in the OW/OB group than in the NW group at 1 month. miR-148a was negatively associated with infant weight, fat mass, and fat free mass, while miR-30b was positively associated with infant weight, percent body fat, and fat mass at 1 month. Maternal obesity is negatively associated with the content of select miRNAs in human milk. An association of specific miRNAs with infant body composition was observed during the first month of life, suggesting a potential role in the infant’s adaptation to enteral nutrition.
Objective. To describe the clinical and serologic manifestations of Sjögren's syndrome (SS) in ethnic groups of the US. Methods. This was a cross-sectional study of 648 patients with primary SS: 20 African American (AA), 164 American Indian (AI), 426 European American (EA), and 38 patients of other races evaluated in a multidisciplinary Sjögren's International Collaborative Clinical Alliance research clinic.Results. AA subjects comprised 3.1% of the SS cohort, much lower than the percentage of AA in the state of Oklahoma (P = 3.01 × E -05), the US (P = 2.24E -13), or a systemic lupus erythematosus (SLE) cohort at the same institution (P = 4.26 × 10E -27). In contrast, the percentage of AI in the SS cohort (25.3%) was much higher than expected (P = 3.17E -09 versus SLE cohort, P = 6.36 -26 versus Oklahoma, and P = 8.14E -96 versus US population). The SS classification criteria were similar between AA and EA, but subjects of AI ancestry had lower rates of abnormal tear and salivary flow, as well as anti-Ro/SSA and anti-La/SSB antibodies. Paradoxically, AIs had higher levels of disease activity (mean ± SD European League Against Rheumatism Sjögren's Syndrome Disease Activity Index score 3.77 ± 4.78) in comparison to EAs (2.90 ± 4.12; P = 0.011) and more extraglandular manifestations affecting mainly the articular and glandular domains. Meanwhile, AA patients were characterized by higher rates of hypergammaglobulinemia (odds ratio [OR] 1.39 [95% confidence interval (95% CI) 1.39-8.65]; P = 0.01), elevated erythrocyte sedimentation rate (ESR) ; P = 0.009), and parotid enlargement ; P = 0.02).Conclusion. AI are affected at high rates with SS but present with few classical features, potentially preventing timely diagnosis. In contrast to SLE, SS is infrequent and not more severe among AA, but the triad of hypergammaglobulinemia, increased ESR, and parotid enlargement warrants extra vigilance for lymphomagenesis.
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, USA). 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=0.50). 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 fulfill pSS criteria have similar rates of fatty infiltration of the minor SG.
Antiviral defenses are inappropriately activated in systemic lupus erythematosus (SLE) and association between SLE and the antiviral helicase gene, IFIH1, is well established. We sought to extend the previously reported association of pathogenic soluble mediators and autoantibodies with mouse Mda5 to its human ortholog, IFIH1. To better understand the role this gene plays in human lupus, we assessed association of IFIH1 variants with soluble mediators and autoantibodies in 357 European-American SLE patients, first-degree relatives, and unrelated, unaffected healthy controls. Association between each of 135 genotyped SNPs in IFIH1 and four lupus-associated plasma mediators, IL-6, TNF-α, IFN-β, and IP-10, were investigated via linear regression. No significant associations were found to SNPs orthologous to those identified in exon 13 of the mouse. However, outside of this region there were significant associations between IL-6 and rs76162067 (p = 0.008), as well as IP-10 and rs79711023 (p = 0.003), located in a region of IFIH1 previously shown to directly influence MDA-5 mediated IP-10 and IL-6 secretion. SLE patients and FDRs carrying the minor allele for rs79711023 demonstrated lower levels of IP-10, while only FDRs carrying the minor allele for rs76162067 demonstrated an increased level of IL-6. This would suggest that the change in IP-10 is genotypically driven, while the change in IL-6 may be reflective of SLE transition status. These data suggest that IFIH1 may contribute to SLE pathogenesis via altered inflammatory mechanisms.
Objective The objective of this study was to assess the performance and reproducibility of the two currently used ocular surface staining scores in the assessment of keratoconjunctivitis sicca in Sjögren syndrome ( SS ) research classification. Methods In a multidisciplinary clinic for the evaluation of sicca, we performed all tests for the American European Consensus Group ( AECG ) and the American College of Rheumatology ( ACR )/European League Against Rheumatism ( EULAR ) classification criteria, including the van Bijsterveld score ( vBS ) and the Ocular Staining Score ( OSS ), in 994 participants with SS or with non‐ SS sicca. We analyzed the concordance between the scores, the diagnostic accuracy and correlation with clinical variables, and interrater and intrasubject reproducibility. Results A total of 308 (31.1%) participants had a discordant vBS and OSS that was due to extra corneal staining points in the OSS . The presence of one or more of the additional points was highly predictive of SS classification (odds ratio = 3.66; P = 1.65 × 10e‐20) and was associated with abnormal results of all measures of autoimmunity and glandular dysfunction. Receiver operating characteristic curves showed optimal cutoff values of four for the vBS (sensitivity = 0.62; specificity = 0.71; Youden's J = 0.33) and five for the OSS (sensitivity = 0.56; specificity = 0.75; Youden's J = 0.31). Notably, there was very poor consistency in interobserver mean scores and distributions ( P < 0.0001) and in intrasubject scores after a median of 5.5 years (35% changed status of the ocular criterion). Conclusion Ocular surface staining scores are useful for SS research classification; however, they are subject to significant interrater and intrasubject variability, which could result in changes in classification in 5%‐10% of all subjects. These results highlight the need for objective and reproducible markers of disease that have thus far remained elusive for SS .
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