OBJECTIVES:Among the myositis specific antibodies (MSAs), the antisynthetase (anti-ARS) and the anti-MDA5 antibodies are those more frequently characterised by the occurrence of joint involvement. We aim to define the prevalence of MSAs in patients with established rheumatoid arthritis (RA), psoriatic arthritis (PsA), or undifferentiated polyarthritis (UPA). METHODS:From January 2021 to December 2024, all RA, PsA and UPA patients prospectively followed in our Early Arthritis Clinic (EAC), were evaluated. Changes in diagnosis, clinical/laboratory signs of muscle/lung/skin involvement at onset or during the follow-up, overlap syndromes, anti-ENA or cytoplasmic ANA positivity, Raynaud's phenomenon, and less than 24 months of follow-up were exclusion criteria. Baseline serum samples were tested for MSAs (line-blot). Positivity was defined according to manufacturers' instructions. RESULTS:143 patients were enrolled (93 females, 65%; 67 AR, 47%; 50 UPA, 35%, 26 PsA, 18%). Line-blot resulted positive in 10 (7%), weak-positive in 12 (8%), and borderline in 26 cases (18%). The remaining 95 patients (67%) were negative. MSAs positivity was anti-cN1A in 3 cases and anti-ARS and anti-MDA in 4 cases each. Weak positivity was found for anti-ARS (4), and anti-PM-Scl75 (3). Borderline results showed a high number of anti-ARS and aMDA5 (12, 46%). No variables were associated with MSA positivity. CONCLUSIONS:MSAs positivity may be observed in one third of patients with primary isolated arthritis. About half of these cases displayed full or weak positivity for MSAs, whereas the remaining half displayed borderline results. Clinicians should be aware that MSA should be assessed only in case of effective clinical need.

ABSTRACT Objective Maternal obesity and excessive weight gain during pregnancy predispose to adverse fetal outcomes and health issues for the offspring. Although maternal lipids play an important role in excess fetal fat accretion, previous studies found heterogeneous results regarding which lipid fraction is most involved in excessive fetal growth in maternal obesity and the role of cord lipids. The aim of this study was to evaluate lipid concentrations in maternal and cord blood in pregnant women with and without obesity and to correlate lipid profile with neonatal and placental biometric parameters. Methods This is a prospective case‐control study comparing 58 pregnant women with and without obesity enrolled from January 2021 to January 2022 at IRCCS Policlinico San Matteo. Lipid profiles at trimesters and in cord blood were tested. Statistical analysis was conducted with a nonparametric rank‐based approach for longitudinal data analysis. Results In both overall and time point analyses, maternal lipid concentrations were higher in participants with obesity than in subjects without obesity. Women with obesity also had higher total cholesterol and triglyceride cord blood concentrations (p < 0.001). Among participants with obesity, neonatal and placental weights were positively correlated with triglycerides and the triglycerides/HDL ratio both in maternal and in cord blood. Finally, among subjects with obesity, maternal and cord blood triglycerides and triglycerides/HDL ratio were significantly higher in large for gestational age (LGA) babies compared to non‐LGA (p < 0.05). Conclusions Compared with controls, obesity in pregnancy is associated with a significant increase in maternal and cord blood lipids, with a positive association between maternal and cord triglycerides and birthweight and placental weight. These findings suggest a further insight into maternal obesity pathophysiology leading to excessive fetal growth, dyslipidemia and insulin resistance in the offspring.

OBJECTIVES:The purpose of our study was evaluate differences in placental histopathology basing on first trimester preeclampsia screening. STUDY DESIGN:Observational case-control study; monocentric enrolment at first trimester ultrasound at the department of Obstetrics and Gynecology of IRCCS Policlinico San Matteo; 278 placental specimen from 234 non-preeclamptic women and 44 preeclamptic women; histopathological examination and evaluation basing on first trimester preeclampsia multiparametric screening; continuous variables were compared by Kruskal-Wallis analysis of variance, categorical variables were compared by Fisher exact test or chi-square test. MAIN OUTCOME MEASURES:Placental lesions prevalence according to first trimester screening result. RESULTS:preeclamptic screen-positive patients had higher frequency of adverse pregnancy outcomes and higher frequency of placental MVM lesions. Screen-positive patients who do not developed preeclampsia had poor maternal and fetal outcomes and higher prevalence of MVM, FVM and placental chronic inflammatory lesions. CONCLUSIONS:Our results shows that the screening identifies pregnancies with placental lesions, which, irrespectively of the development of preeclampsia, correlate with impaired fetal growth and poor pregnancy outcomes. The presence of MVM, FVM and VUE in patients at high risk for preeclampsia reflects the need for close clinical follow-up during pregnancy due to the increased risk of adverse outcomes.

Objective To delineate, within the framework of current clinical practice and criteria, the sustainability of first-line immuno-suppressive treatment discontinuation in rheumatoid arthritis (RA) and the impact of residual disease in remission on long-term drug-free (DF) outcomes.Methods RA patients, referring to the Pavia early arthritis clinic (EAC) between 2009 and 2021 and achieving remission after Disease Activity Score-driven methotrexate (MTX) monotherapy, were recruited. Eligible patients underwent DF follow-up at 3-month intervals over 5 years after MTX discontinuation. Pre-selected clinical, serological and ultrasound (US) exposure variables at MTX withdrawal were analysed using multivariable Cox regression to predict time-to-flare.Results Of 761 EAC patients with RA, 132 started DF follow-up (person-months: 3678). 62 experienced a flare after a median (range) of 9 (3–60) months, resulting in a progressive decline in flare-free survival throughout the observation period. Whole-cohort multivariate Cox regression identified anti-citrullinated protein antibody (ACPA) positivity (HR: 4.20, 95% CI 2.37 to 7.44) and hands’ joints with grey scale (US-GS) alterations (GS>1; HR: 2.18, 95% CI 1.20 to 3.93) as independent predictors. ACPA-positive patients in Simplified Disease Activity Index (SDAI) remission displayed a flare-free survival estimate at 5 years of 6.4% (95% CI 1.2 to 35.7) versus 78.2% (95% CI 67.4 to 90.8) for ACPA-negative patients in SDAI remission without residual US-GS alteration in hands’ joints (n=59); the latter group showing no evidence of radiographic progression and functional deterioration.Conclusions Long-term DF remission is attainable in a niche subset of ACPA-negative RA. Examining clinical and subclinical residual synovial abnormalities during remission allows for effective preemptive identification of this subset in real life.

Objective The CLASS (Classification Criteria of Anti-Synthetase Syndrome) project is a large international multicentre study that aims to create the first data-driven anti-synthetase syndrome (ASSD) classification criteria. Identifying anti-aminoacyl tRNA synthetase antibodies (anti-ARS) is crucial for diagnosis, and several commercial immunoassays are now available for this purpose. However, using these assays risks yielding false-positive or false-negative results, potentially leading to misdiagnosis. The established reference standard for detecting anti-ARS is immunoprecipitation (IP), typically employed in research rather than routine autoantibody testing. We gathered samples from participating centers and results from local anti-ARS testing. As an "ad-interim" study within the CLASS project, we aimed to assess how local immunoassays perform in real-world settings compared to our central definition of anti-ARS positivity. Methods We collected 787 serum samples from participating centres for the CLASS project and their local anti-ARS test results. These samples underwent initial central testing using RNA-IP. Following this, the specificity of ARS was reconfirmed centrally through ELISA, line-blot assay (LIA), and, in cases of conflicting results, protein-IP. The sensitivity, specificity, positive likelihood ratio and positive and negative predictive values were evaluated. We also calculated the inter-rater agreement between central and local results using a weighted kappa co-efficient. Results Our analysis demonstrates that local, real-world detection of anti-Jo] is reliable with high sensitivity and specificity with a very good level of agreement with our central definition of anti-Jo] antibody positivity. However, the agreement between local immunoassay and central determination of anti-non-Jo] antibodies varied, especially among results obtained using local LIA, ELISA and "other" methods. Conclusion Our study evaluates the performance of real-world identification of anti-synthetase antibodies in a large cohort of multi-national patients with ASSD and controls. Our analysis reinforces the reliability of real-world anti-Jo] detection methods. In contrast, challenges persist for anti-non-Jo] identification, particularly anti-PL7 and rarer antibodies such as anti-OJ/KS. Clinicians should exercise caution when interpreting anti-synthetase antibodies, especially when commercial immunoassays test positive for non-anti-Jo] antibodies.

OBJECTIVES:Although antisynthetase antibodies (ARS) are the established markers of the so-called antisynthetase syndrome (ASSD), in these patients the concomitant positivity of anti-Ro52 antibodies, reported in up to the 50% of cases, is not rare. Several studies focused on the effect of different ARS specificities on the evolution of ASSD, the most recent showing no effects. On the contrary, the role of co-occurring anti-Ro52 antibodies in ASSD is still debated. We investigated the potential of anti-Ro52 antibodies in identifying a clinical phenotype of ASSD or influencing prognosis, irrespectively to the underlying ARS specificity.METHODS:Retrospective analysis of clinical, imaging and laboratory characteristics, therapeutic approaches and outcome at baseline and at last follow-up, of 60 ASSD patients progressively enrolled at our Hospital.RESULTS:We identified 34 anti-Ro+ and 26 anti-Ro- ASSD patients. Classic triad prevalence at baseline was similar between the two groups, whereas interstitial lung disease (ILD) (p value=0.01) and myositis (p value=0.03) were significantly more prevalent in anti-Ro52+ and in anti-Ro52- patients at last follow up, respectively. No differences in therapeutic approaches, oxygen need and ILD patterns were observed. Overall mortality was 25% (15 subjects). No differences in mortality, overall and disease related, between anti-Ro52+ and anti-Ro52- patients were observed (p value=0.764), despite the more frequent ILD occurrence in anti-Ro52+ patients. Survival curves were not different at any time point (Log-rank test, p value 0.98).CONCLUSIONS:Anti-Ro52 antibodies affect time course and clinical characteristics of ASSD. Although ILD is significantly more associated to anti-Ro52 antibodies, no difference in mortality was observed compared to anti-Ro52 negative patients.

The aim of the study was to evaluate the rate of obstetric complications and the burden of obstetric outcomes in antiphospholipid syndrome (APS), non-criteria APS and asymptomatic antiphospholipid antibodies (aPL) carriers. From 2013-2018, 163 pregnant subjects with aPL antibodies and 785 controls were enrolled. Penalized logistic regression was used to compare obstetric complications. Cases included 62 complete APS (38 %), 48 non-criteria APS (29.4 %) and 53 (32.5 %) asymptomatic aPLcarriers. Connective tissue diseases (CTDs) were diagnosed in 31.3 % of cases. The rate of high-risk aPL profile was higher (p < .01) in APS (67.7 %) compared to non-criteria (14.6 %) and aPL-carriers (9.4 %). Double/ triple positivity was 33.9 % (p < .05 compared to non-criteria and aPL-carriers) in APS, 10.4 % in non-criteria and 9.4 % in aPL-carriers. The rate of adverse pregnancy outcomes were 5.6 % in controls, 41.9 % (adj.OR = 6.95 %CI = 2.7-13.5) in APS, 25 % (adj.OR = 4.4,95 %CI = 2-9.4) in non-criteria and 28.3 % (OR = 4.95 %CI = 1.8-8.8) in aPL-carriers. CTDs were independently associated with an increased risk of adverse obstetric outcomes (OR = 2.8,95 %CI = 1.36-5.89). The attributable fraction (AF) of adverse obstetric events was higher among low-risk antibodies compared to high-risk (AF = 0.27,95 %CI = 0.22-0.31 vs AF = 0.16,95 %CI = 0.16-0.2,p < .01) and among single positivity compared to double/triple positivity (AF = 0.32,95 %CI = 0.26-0.37 vs AF = 0.11,95 %CI = 0.09-0.13,p < .01) suggesting that low-risk subjects are responsible for a high burden of obstetric complications.

Interstitial lung disease (ILD) encompasses a wide range of parenchymal lung pathologies with different clinical, histological, radiological, and serological features. Follow-up, treatment, and prognosis are strongly influenced by the underlying pathogenesis. Considering that an ILD may complicate the course of any connective tissue disease (CTD) and that CTD's signs are not always easily identifiable, it could be useful to screen every ILD patient for a possible CTD. The recent definition of interstitial pneumonia with autoimmune features is a further confirmation of the close relationship between CTD and ILD. In this context, the multidisciplinary approach is assuming a growing and accepted role in the correct diagnosis and follow-up, to as early as possible define the best therapeutic strategy. However, despite clinical advantages, until now, the pathways of the multidisciplinary approach in ILD patients are largely heterogeneous across different centers and the best strategy to apply is still to be established and validated. Aims of this article are to describe the organization of our multidisciplinary group for ILD, which is mainly focused on the early identification and management of CTD in patients with ILD and to show our results in a 1 year period of observation. We found that 15% of patients referred for ILD had an underlying CTD, 33% had interstitial pneumonia with autoimmune feature, and 52% had ILD without detectable CTD. Furthermore, we demonstrated that the adoption of a standardized strategy consisting of a screening questionnaire, specific laboratory tests, and nailfold videocapillaroscopy in all incident ILD proved useful in making the right diagnosis.

Response to: 'Pitfalls of antinuclear antibody detection in systemic lupus erythematosus: the positive experience of a national multi-center study' by Pregnalato et alWe appreciate the comments by Pregnolato et al 1 on our original paper 2 and subsequent correspondence in the journal. 3 4 The data presented are very interesting and suggest that, under certain circumstances, results of antinuclear antibody (ANA) testing with samples from patients with established systemic lupus erythematosus can show both a high frequency of positivity and high concordance among testing laboratories.Such agreement may result from the nature of the samples themselves, including the titre of the antibodies and the array of specificities present, the kits used for the assays and the experience and training of the observers.While we would acknowledge that ANA assays can perform very well, our experience as well as that in the literature indicates that variability occurs significantly in a way that complicates screening of patients for clinical trials.Notwithstanding the demonstrations of the kind reported by Pregnolato et al, we think that it is important to try to understand assay variability and improve serological determinations for both routine care as well as clinical research.

OBJECTIVES:To evaluate if the timing of appearance with respect to disease onset may influence the arthritis presentation pattern in antisynthetase syndrome (ASSD).METHODS:The patients were selected from a retrospective large international cohort of ASSD patients regularly followed-up in centres referring to AENEAS collaborative group. Patients were eligible if they had an antisynthetase antibody testing positive in at least two determinations along with arthritis occurring either at ASSD onset (Group 1) or during the course of the disease (Group 2).RESULTS:445 (70%; 334 females, 110 males, 1 transsexual) out of the 636 ASSD we collected had arthritis, in the majority of cases (367, 83%) from disease onset (Group 1). Patients belonging to Group 1 with respect to Group 2 had an arthritis more commonly polyarticular and symmetrical (p=0.015), IgM-Rheumatoid factor positive (p=0.035), erosions at hands and feet plain x-rays (p=0.036) and more commonly satisfying the 1987 revised classification criteria for rheumatoid arthritis (RA) (p=0.004). Features such as Raynaud's phenomenon, mechanic's hands and fever (e.g. accompanying findings) were more frequently reported in Group 2 (p=0.005).CONCLUSIONS:In ASSD, the timing of appearance with respect to disease onset influences arthritis characteristics. In particular, RA features are more common when arthritis occurs from ASSD onset, suggesting an overlap between RA and ASSD in these patients. When arthritis appears during the follow-up, it is very close to a connective tissue disease-related arthritis. Also, the different prevalence of accompanying features between these two groups is in line with this possibility.

OBJECTIVE:Villous atrophy (VA) of the small bowel is mainly related to coeliac disease (CD), whose diagnosis is made on the basis of positive endomysial/tissue transglutaminase antibodies while on a gluten-containing diet in the vast majority of patients. However, VA can also occur in other conditions whose epidemiology is little known. Our aim was to study the epidemiology and clinical features of these rare enteropathies.PATIENTS AND METHODS:Clinical and laboratory data of all the patients with VA directly diagnosed in our centre in the last 15 years were collected and statistically analysed.RESULTS:Between September 1999 and June 2015, 274 patients were diagnosed with VA. A total of 260 patients were also positive to coeliac antibodies; the other 14 had VA, but no IgA endomysial antibodies: five had common variable immunodeficiency, three had dermatitis herpetiformis, two had IgA deficiency associated with CD, one had abdominal lymphoma, one had unclassified sprue, one had olmesartan-associated enteropathy and one had seronegative CD. Mortality was 6.0 deaths per 100 person years (95% confidence interval: 2.2-16) in patients with VA but negative coeliac antibodies, whereas only 0.2 deaths per 100 person years (95% confidence interval: 0.1-0.6) occurred in coeliac patients.CONCLUSION:Patients with VA and negative endomysial antibodies are rare. However, these forms of VA identify specific causes that can be diagnosed. These patients are affected by a very high mortality.

Objective To evaluate the impact of preclinical systemic autoimmune rheumatic disorders on pregnancy outcome. Methods In this longitudinal cohort study, patients were enrolled during the first trimester of pregnancy if they reported having had connective tissue disorder symptoms, were found to be positive for circulating autoantibodies, and on clinical evaluation were judged to have a preclinical or incomplete rheumatic disorder. The incidence of fetal growth restriction (FGR), preeclampsia, and adverse pregnancy outcomes in patients with preclinical rheumatic disorders was compared with that in selected controls, after adjustment for confounders by penalized logistic regression. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. Results Of 5,232 women screened, 150 (2.9%) were initially diagnosed as having a suspected rheumatic disorder. After a mean ± SD postpartum follow‐up of 16.7 ± 5.5 months, 64 of these women (42.7%) had no clinically apparent rheumatic disease and 86 (57.3%) had persistent symptoms and positive autoantibody results, including 10 (6.7%) who developed a definitive rheumatic disease. The incidences of preeclampsia/FGR and of small for gestational age (SGA) infants were 5.1% (23 of 450) and 9.3% (42 of 450), respectively, among controls, 12.5% (8 of 640) (OR 2.7 [95% CI 1.1–6.4]) and 18.8% (12 of 64) (OR 2.2 [95% CI 1.1–4.5]), respectively, among women with no clinically apparent disease, and 16.3% (14 of 86) (OR 3.8 [95% CI 1.9–7.7]) and 18.6% (16 of 86) (OR 2.3 [95% CI 1.2–4.3]), respectively, among those with persisting symptoms at follow‐up. Mean ± SD umbilical artery Doppler pulsatility indices were higher among women with no clinically apparent disease (0.95 ± 0.2) and those with persisting symptoms (0.96 ± 0.21) than in controls (0.89 ± 0.12) ( P = 0.01 and P < 0.001, respectively). Conclusion In our study population, preclinical rheumatic disorders were associated with an increased risk of FGR/preeclampsia and SGA. The impact of these findings and their utility in screening for FGR/preeclampsia need to be confirmed in population studies.

The burden of pregnancy complications associated with well defined, already established systemic rheumatic diseases preexisting pregnancy such as rheumatoid arthritis, systemic lupus erythematosus or scleroderma is well known. Systemic rheumatic diseases are characterized by a long natural history with few symptoms, an undifferentiated picture or a remitting course making difficult a timely diagnosis. It has been suggested that screening measures for these diseases could be useful but the impact of unrecognized systemic rheumatic disorders on pregnancy outcome is unknown. The objective of the study was to evaluate the impact of previously unrecognized systemic autoimmune rheumatic on the incidence of preeclampsia and fetal growth restriction (FGR).

Background: Emerging research on the mechanisms of disease chronicity in experimental arthritis has included a new focus on the draining lymph node (LN). Here, we combined clinical-serological analyses and power Doppler ultrasound (PDUS) imaging to delineate noninvasively the reciprocal relationship in vivo between the joint and the draining LN in patients with rheumatoid arthritis (RA).Methods: Forty consecutive patients refractory to conventional synthetic disease-modifying anti-rheumatic drugs were examined through parallel PDUS of the hand-wrist joints and axillary LNs and compared with 20 healthy subjects. A semiquantitative score for LN gray-scale (GS) parameters (nodal hypertrophy and cortical structure) and LN PD signal was developed. A 6-month follow-up study with serial sonographic assessments was then performed on initiation of tumor necrosis factor (TNF) inhibitors.Results: PDUS analysis of RA axillary LNs revealed the existence of marked inter-individual heterogeneity and of quantitative differences compared with healthy individuals in both GS and PD characteristics. RA LN changes were plastic, responsive to anti-TNF treatment, and displayed a degree of concordance with synovitis activity in peripheral joints. However, low LN PD signal at baseline despite active arthritis was strongly associated with a poor clinical response to TNF blockade.Conclusions: PDUS analysis of the draining LN in RA allows capture of measurable inter-individual differences and dynamic changes linked to the underlying pathologic process. LN and joint sonographic assessments are nonredundant approaches that may provide independent perspectives on peripheral disease and its evolution over time.

Objective: To investigate the rates and coexistence of autoimmune thyroid and connective tissue diseases (CTD) during the first trimester of pregnancy and their influence on pregnancy outcome. Study design: A cohort study of 150 women with CTD diagnosed during first trimester of pregnancy and 150 negative controls.Main outcome measures: Screening of CTD by a self-reported questionnaire, rheumatic and thyroid autoantibody detection, clinical rheumatological evaluation and obstetric outcomes.Results: Out of 3852 women screened, 61 (1.6%) were diagnosed with undefined connective tissue disease (UCTD), 28 (0.7%) with major CTD (six rheumatoid arthritis, five systemic lupus erythematosus, eight Sjogren syndrome, five anti-phospholipid syndrome, two systemic sclerosis, one mixed CTD and one monoarticular arthritis) and 61 (1.6%) had insufficient criteria for a diagnosis of a rheumatic disease. The overall prevalence of either thyroid peroxidase (TPO-a) or thyroglobulin (TG-a) autoantibodies detection was 8% (12/150) among controls, 62.3% (38/61) among UCTD and 60.7% (17/28) in women with a major LTD (p<.001 compared to controls for both comparisons). After adjustment for confounders, overall CTDs (major or undefined) (OR = 3.54, 95% CI; 1.61-7.78) and TPO-a plus TG-a positivity (OR = 2.78, 95% CI;1.29-5.98) were independently associated with increased risks of moderate-severe complications of pregnancy (miscarriage, fetal growth restriction, preeclampsia, delivery before 34 weeks).Conclusions: Rheumatic and thyroid autoantibodies during pregnancy are closely associated. Thyroid antibodies could add to the risk of adverse pregnancy outcome associated with connective tissue diseases. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

Objective: To investigate the presence of autoimmune rheumatic disorders among women with autoimmune thyroid disorders diagnosed during the first trimester of pregnancy and subsequent pregnancy outcomes.Design: Case-control study.Setting: Tertiary obstetric and gynecologic center.Patient(s): Pregnant women in the first trimester of pregnancy.Intervention(s): Clinical, laboratory, ultrasonographic evaluations.Main Outcome Measure(s): Thyroid-stimulating hormone (TSH) level; antibodies against thyroperoxidase, thyroid globulin and TSH receptor detection; screening for rheumatic symptoms and antinuclear antibodies (ANA); uterine artery pulsatility index evaluation; pregnancy complication onset.Result(s): Out of 3,450 women enrolled, 106 (3%) were diagnosed with autoimmune thyroid disorders. ANA were present in 18 (16.9%) of 106 cases and 26 (12.6%) of 206 controls. Of the cases, 28 (26.4%) of 106 reported rheumatic symptoms, 5 of these were diagnosed with Sjogren syndrome or with undefined connective tissue disease. Autoimmune thyroid diseases are statistically significantly associated with a higher risk of preeclampsia, fetal growth restriction, and overall pregnancy complications compared with controls, with a higher uterine artery pulsatility index, suggesting a defective placentation in thyroid disorders. The effect of ANA-positivity on moderate/severe adverse pregnancy outcomes was statistically significant among the patients with thyroid disorders (9 of 18 as compared to 8 of 88, odds ratio 9.65; 95% confidence interval, 2.613-7.81).Conclusion(s): Connective tissue diseases are frequently associated with autoimmune thyroid disorders diagnosed during the first trimester of pregnancy. Thyroid autoimmunity and ANA positivity independently increased the risk of adverse pregnancy outcomes. (C) 2015 by American Society for Reproductive Medicine.

Autoimmune rheumatic diseases in pregnancies are associated with increased adverse obstetric outcomes. We compared maternal soluble human leucocyte antigen-G (sHLA-G) blood levels in subjects with a rheumatic disease preexisting pregnancy and unaffected controls. Third-trimester blood maternal sHLA-G concentrations were significantly higher in subjects with rheumatic diseases than in controls (mean 93.1ng/ml [SD 42.1] vs 58.1ng/ml [SD 96.3], p=0.003). Cord blood sHLA-G concentrations were significantly higher in rheumatic disease than in those born to control mothers (median 41.2ng/ml [IQR: 3.3-44.0] vs 17.9ng/ml [IQR: 17.2-88.1], p=0.007). A strict positive correlation (r=0.88, p<0.001) was found between the maternal and fetal titers of ANA autoantibodies as well as between maternal and fetal sHLAG circulating levels (r=0.58 and r=0.67, respectively, for controls and cases, p<0.001). Maternal s-HLA-G blood concentrations were significantly higher in subjects with rheumatic disease DEL/DEL homozygous for a polymorphism of the 3' untranslated regulatory region of HLA-G (HLA-G 14bp) than in the corresponding healthy controls (mean values 141.5ng/ml [SD: 166] vs 54.2ng/ml [SD: 35], p=0.009). Increasing maternal and cord blood levels of s-HLA-G concentrations among pregnant subjects with rheumatic diseases compared with controls suggest that autoimmune diseases prompt a maternal and fetal immune response that favors pregnancy immune tolerance.