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Background and Aims

Concerns were raised whether patients with connective tissue diseases (CTD) can mount a protective immune response to mRNA vaccines against SARS CoV2 and whether the vaccination may trigger a flare up of the CTD.

Our aims were to assess the impact on CTD activity and the humoral response to 2 doses of mRNA vaccine against SARS CoV2, in CTD patients treated with immunomodulating drugs.

Methods

Consecutive 90 CTD patients treated at our rheumatology institute who received their first SARS-CoV-2 (Pfizer) vaccine were recruited to the study. They were reassessed 4-6 weeks after receiving the second dose of vaccine and blood samples were obtained for serology. CTD activity assessment and the vaccine side effects were documented during both visits. Neutralizing IgG Antibodies (Ab) against the spike receptor-binding domain of SARS COV2 virus were detected using the SARS-Cov-2 IgG II Quant (Abbott) assay.

Results

The cohort included 51systemic sclerosis patients, 24 with lupus, 9 with myositis, 3 with Sjogren and 3 with mixed CTD ((mean age(SD) 55(14), disease duration 9.4(5.7)). The immunomodulatory treatment was continued. 69 % received csDMARDs, 35% biological DMARDs, 18% combined therapy (csDMARDs+bDMARDs) and 42% steroids. 72 patients (80%) mounted a significant humoral response (median(IQR) 3738.5(80-40000)AU/ml). The humoral response was influenced only by the type of treatment (especially rituximab). The CTD remained stable.

Conclusions

The vast majority of CTD patients developed a significant humoral response to 2 doses of the Pfizer mRNA vaccine against SARS CoV2 virus. Only minor side effects were reported, no apparent impact on CTD activity was noted.

Background and Aims

The association between environmental air pollution and osteoporosis is unclear. The aim of the present study is to determine the association between osteoporosis and air pollution.

Methods

We conducted a retrospective analysis of a nation-wide cohort (DeFRACalc79 database). DeFRACalc79 is a tool that estimates the fracture risk considering clinical and densitometric risk factors. Data on daily air pollution concentrations were retrieved from the ISPRA Institute (Italian institute for air quality). Associations between continuous variables were tested using Pearson correlation coefficients for normally distributed variables or Spearmen rank test for non-normally distributed tests and binary logistic regressions.

Results

59,950 women (mean age 65.1 years, SD 10.9 years) were included in the study. Exposure to pollutants (particulate matter [PM] less than 10 μm and PM less than 2.5 μm) was estimated based on more than 3,000,000 daily measurements (urban, industrial, and rural zones) from 2013 to 2019. We found a significant negative association between femoral neck BMD and air pollution exposure (unadjusted ρ -0.032 for PM 10 and ρ-0.056 for PM 2.5, p<0.0001). The adjusted model (binary logistic regression including covariates such as age, BMI, glucocorticoid intake and comorbidities) showed that every 1 μg/m3 increase in PM 10 the risk of osteoporosis at any site increased by 0.05% and every 1 μg/m3 increase in PM 2.5 the risk of osteoporosis at any site increased by 1.0% Patients exposed to PM10 >30 μg/m3 had a 15% increased risk of having osteoporosis (aOR 1.15 95%CI 1.14-1.19).

Conclusions

Air pollution is associated with an increased risk of osteoporosis.

Background and Aims

Proinflammatory cytokines play critical role in the pathophisology of rheumatoid arthritis (RA). Recent studies concerning IL-8 support its role in ACPA-mediated osteoclast activation as a mechanism of arthralgia and bone loss, but the functional involvement of this cytokine are still uninvestigated. This analysis aimed to determine the association of IL-8 cytokine levels with clinical variables in patients with RA.

Methods

63 patients with RA and 25 patients in control group were included in this study. The cytokines levels in serum were evaluated by the ProcartaPlex immunoassays kits (eBioscience, Affymetrix) on the Luminex xMAP system according to manufacturer’s instruction.

Results

IL-8 was elevated in RA patient group (p<0.0001). We found differences between control group and RA activity groups according to Disease Activity Score in 28 joints (Figure1.).

Figure 1. IL-8 concentration in RA and healthy control. Blue line connects medians.

IL-8 was also positively correlated with C-reaction protein (r=0,43), erythrocyte sedimentation rate (r=0,4), level of autoantibodies (RF: r=0,54; ACPA: r=0,51). Furthermore there was correlation between IL-8 and number of swollen (r=0.38) and painfull joints (r=0.33).

Conclusions

Circulating IL-8 is correlated with disease activity and ACPA, therefore may impact the pathogenesis and progression of RA and may be the point of further investigations.

Background and Aims

Polyautoimmunity (PolyA) is defined as the presence of more than one autoimmune disease (AD) in a single patient and Systemic Lupus Erythematosus (SLE) is one of the most frequently involved AD. The aim of this study was to describe an estimated prevalence of PolyA in a Colombian-single center Systemic Lupus Erythematosus cohort and to analyze the presumable associated factors for PolyA.

Methods

This was a cross sectional study. All patients with SLE at our specialized rheumatology center from January 2015 to December 2020 were identified. All consecutive patients fulfilling SLICC/2012 criteria were analyzed. Data recorded included demographics, SLE and PolyA characteristics, laboratory, and treatments. Biostatistical methods included bivariate and multivariate analyses (binary logistic regression) to identify the factors associated with PolyA (p-value <0.05, SPSS V20).

Results

A total of 480 fulfilled SLICC/2012 criteria (422 females, mean age 47.7±15.3 years, mean duration of disease 11.24±8.9 years). There were 161/463 (33.5%) patients with PolyA of which 16.8% had 2 or more AD (i.e., Multiple Autoimmune Syndrome). The most frequent PolyA were antiphospholipid syndrome (47.8%), Sjögren’s syndrome (30.4%) and Systemic sclerosis (10.6%). PolyA patients were older, had higher age at onset, longer duration of disease (bivariate analysis) and less renal compromise (multivariate analysis). There were additional associated factors identified through the bivariate and multivariate models (Figure-table).

Conclusions

Near a third of SLE patients had PolyA. This was significantly associated with venous thrombosis, sicca symptoms and APS antibodies. An inverse association with lupus nephritis was found. This could encourage additional research evaluating PolyA associations in different populations.

Background and Aims

Autoimmune Diabetes Mellitus (ADM) is an autoimmune metabolic disorder characterized by chronic hyperglycemia, presence of autoreactive T and B cells and autoantibodies against self-antigens. A membrane-bound enzyme on the pancreatic beta-cells, GAD 65, is one of the main autoantigens in type 1 diabetes. Autoantibodies against GAD65 are potentially involved in beta-cells destruction and decline of pancreatic functions.

The human complement receptor type 1 (CR1) on B- and T-lymphocytes has a suppressive activity on these cells. We hypothesized that it may be possible to eliminate GAD65-specific B cells from ADM patients by using chimeric molecules, containing an anti-CR1 antibody, coupled to peptides resembling GAD65 B/T epitopes. These molecules are expected to bind selectively the anti-GAD65 specific B-cells by the co-crosslinking of the immunoglobulin receptor and CR1 and to deliver a suppressive signal.

Methods

Two synthetic peptide epitopes derived from GAD65 protein, and anti-CD35 monoclonal antibody were used for the construction of two chimeras. The immunomodulatory activity of the engineered antibodies was tested in vitro (Epitope prediction, Protein engineering, ELISA, FACS, ELISpot and Proliferation assay) and in vivo (NSG mice transfer) using PBMCs from diabetes patients.

Results

A reduction in the number of anti-GAD65 IgG antibody-secreting plasma cells and increased percentage of apoptotic B lymphocytes was observed after treatment of PBMCs from patients with ADM with engineered antibodies.

Conclusions

The constructed chimeric molecules are able to modulate selectively the activity of GAD65-specific B-lymphocytes and the production of anti-GAD65 IgG auto-antibodies by co-crosslinking of the inhibitory CR1 and the BCR.

Background and Aims

The epidemiology of idiopathic inflammatory myopathies (IIMs) has been extensively studied out of Africa, but remains unclear in Africa. This is the first systematic review extensively addressing the epidemiology of IIMs in Africa.

Methods

We searched MEDLINE, EMBASE and African Journals Online for relevant studies published through December 30, 2020 . Data were combined via narrative synthesis. The review protocol was registered with PROSPERO, CRD42020186781.

Results

Of 9918 records, 39 were included, reporting 683 cases (71.7% adults). The incidence of dermatomyositis (DM) was estimated at ~7.5/1,000,000 person years and 1.2/1,000,000 person years, and that of polymyositis (PM) was estimated at 8.8/1,000,000 person years. Prevalence rates of IIMs and PM subtype were estimated at 11.49/100,000 and 11/100,000 (95% confidence interval: 0-32), respectively. Mean age at diagnosis ranged from 7.9 to 57.2 years, and the female proportion from 50% to 100%. Main subtypes of IIMs in adults were DM (21%-93%) and PM (12%-79%), whereas DM (5.8%-9%) was the commonest juvenile IIM. Skeletal muscle involvement (56%-100%) was the main disease feature, and oesophagus the most commonly affected internal organ (6%-65.2%). Anti-Jo1/histidyl tRNA synthetase (7%-100%) and anti-Mi2 (17%-45%) antibodies were the commonest myositis specific antibodies. Early mortality was high (7.8%-45%); main death causes being infections, cancers and damage accrual in respiratory and cardiovascular domains.

Conclusions

The epidemiology of IIMs in Africa seems similar to that from other continents, except for a potential much younger age at onset of adult IIMs in Africa. Further high-quality studies are needed.

Background and Aims

Antiphospholipid antibodies (aPL) can induce fetal loss in experimental animal models. Human studies did find hypocomplementemia associated to pregnancy complications in patients with Antiphospholipid Syndrome (APS), but these results are not unanimously confirmed. We have then performed a multicenter study to identify if preconception decreased C3 and/or C4 levels could be considered a risk factor for adverse pregnancy outcome (APO) in APS and aPL carriers pregnancies.

Methods

We performed a multicenter study including 503 pregnancies from 11 Italian and 1 Russian Centers. Data in women with APS and asymptomatic carriers with persistently positive aPL and preconception complement levels were available for 260 pregnancies.

Results

93 (36%) of all pregnancies had low levels of preconception C3 (51, 55, %) or C4 (13, 14%) or both (29, 31%). 167 (64%) pregnancies had normal complement levels. In pregnancies with low preconception C3/C4, a significantly higher prevalence of pregnancy losses was observed (p=0.008). A subgroup analysis focusing on triple aPL positive patients found out that preconception low C3 and/or C4 levels was associated with an increased rate of pregnancy loss (p=0.05) as shown in Table 1.

Conclusions

Our findings confirm that decreased complement levels before pregnancy are associated with increased risk of APO. Pregnancy losses has been seen only in women with triple aPL positivity, indeed single or double positivity does not show this trend. Complement levels are cheap and easy to be measured therefore they could represent a useful aid to identify patients at increased risk of pregnancy loss.

Background and Aims

Pregnant women with autoimmune diseases (AIDs) have higher probabilities of maternal and fetal complications. AIDs have a variable behavior during pregnancy: while some improve, others remain stable and several worsen with associated poor obstetric and perinatal outcomes. The aim of this study was to describe AIDs and obstetric outcomes in pregnant women.

Methods

This is a retrospective study carried out between 2011-2020 in Cali, Colombia. Pregnant women with diagnosis of AIDs were included. Demographic, clinical and laboratory features, as well as obstetric and fetal outcomes including intensive care unit (ICU) characteristics were evaluated.

Results

Fifty-six pregnant women with AIDs were included. Mean age was 29.6 (4.9%) years. Fourty-eight (85.7%) patients had Systemic Lupus Erythematosus (SLE), of which five had polyautoimmunity; six (10.7%) had antiphospholipid syndrome; one (1.8%) rheumatoid arthritis, and one (1.8%) inflammatory myopathies. Diagnosis was made before pregnancy in 41 (73.2%) with an average duration of disease of 56.6 (53.9) months. Of SLE patients, 13/48(27.1%) presented lupus nephritis. Preterm labor (38, 67.9%), preeclampsia (28, 50%), prelabor rupture of membranes (11, 19.6%), were the most common complications. Twenty-two (39.3%) patients required ICU; 40,9% of them due to AID activity, 27.3% for cardiovascular damage, 9.1% for septic shock, and 9,1% for acute kidney failure. Fetal survival was 80.4% (N=45/56). Two were diagnosed with neonatal lupus and two with congenital heart block. One maternal death was registered due to preeclampsia and intraventricular hemorrhage.

Conclusions

This is the first description of AIDs during pregnancy in Colombia.

Background and Aims

Presence of antithyroid antibodies is an independent risk factor for pregnancy complications. In this regard, the revealing mechanisms of the antithyroid antibodies influence on placental development is a relevant task.

The aim of the study was to assess the expression of MCL1, which is an anti-apoptotic factor, in the murine placentas after administration of anti-thyroperoxidase antibodies.

Methods

IgG from patients with AIT were injected in mice on the 4^th pregnancy day. The titer of antibodies to thyroperoxidase exceeded 1000 U/ml while anti-thyroglobulin and anti-phospholipid antibodies were excluded in these samples. The control group received commercial human IgG. Pregnancy outcomes were evaluated. Immunohistochemical analysis of the MCL1 expression in the placentas was performed.

Results

In the group of mice that received anti-thyroperoxidase antibodies were obtained 70 viable fetuses. In the control group – 195 viable fetuses (p<0.05). The average weight of fetuses and placentas in the studied group was 351 mg and 112 mg, while in the control group - 503 mg and 125 mg, respectively (p<0.05). The IHC assessment revealed a significant decrease in the MCL1 expression in placentas of mice that received anti-TPO antibodies 29.24±1.06% vs 38.57±0.79% in control group (p<0.01).

Conclusions

The decrease in the number of viable fetuses and in the weight of fetuses and placentas after the administration of anti-thyroperoxidase antibodies may be related with the activation of apoptosis in the murine placentas. This might be due to insufficient influence of anti-apoptosis factors, which confirmed by the decrease in the MCL1 expression.

The study supported by a grant 14.W03.31.0009

Background and Aims

Psoriatic arthritis (PsA) is an infammatory arthritis with distinct phenotypic subtypes. Enthesitis is assigned as a hallmark of the disease, given its signifcant relations to disease activity and patient-reported outcomes (PROs). Our aim is to evaluate the prevalence of enthesitis and its association with some clinical parameters, particularly quality of life (QoL) in PsA patients (pts).

Methods

187 (M/F=97 (50.2%)/90(48.8%) PsA pts fulfilling the CASPAR criteria were included. Mean age 45.6±11.7 years (yrs), DAPSA 21.05±21.03, median (Me) PsA duration 88 [16;421] mo. All pts underwent standard clinical examinations and PROs (EQ-5D, PsAID12, HAQ, BASDAI, FACIT-F) Analysis were performed in 2 groups: enthesitis positive (42.3%) and enthesitis negative (57.7%), for assess enthesitis in PsA pts used Leeds Enthesitis Index (LEI), using parametric and non-parametric tests as appropriate.

Results

When 79 (42.3%) patients with enthesopathy and 108 patients (57.7%) without enthesopathy were compared, patients with enthesitis had more disease activity 40.7±23.3 vs 20.9±18.7 respectively). TJC, SJC, VAS, HAQ, BASDAI, PsAID-12 were signifcantly better in pts without enthesitis (p < 0.05 for all). The comparison of clinical parameters of pts with and without enthesitis is given in Table 1. Moreover, significant but weak positive correlations between the LEI score and TJC, DAPSA, BASDAI, and negative correlations with EQ-5D and FACIT-F were found (p < 0.005 for all) (Table 2).

Conclusions

In PsA pts reported that with enthesitis is associated with greater PsA disease activity and worse functional status and QoL.

Background and Aims

Secukinumab effectiveness has been demonstrated in both psoriasis (PsO) and psoriatic arthritis (PsA). However, it is unknown whether arthritis, compared to PsO alone, may represent a risk factor for withdrawal. Our aim was to identify predictors of secukinumab survival, including the presence of arthritis, in PsO and PsA.

Methods

Consecutive PsO and PsA patients initiating secukinumab were enrolled and followed-up every 6 months, up to 24-months or discontinuation. Medical history, disease activity indices and Body Mass Index (BMI) were collected. Kaplan-Meier curves and log-rank test were used to analyze differences in drug survival according to sex, BMI, biological therapy line in the whole population (psoriatic disease) and separately for PsO/PsA. A multivariable Cox-regression model was built to assess whether presence of arthritis (main independent variable) may influence drug survival by having time-to-secukinumb-discontinuation as outcome. Results were expressed as Hazard Ratio (HR) and 95% Confidence Interval (95%CI).

Results

Sixty-two PsO and 90 PsA patients were enrolled (Table). Retention rate was 77% and 59% at 12- and 24-months. In the whole population, naïve patients displayed higher drug survival (log-rank=4.06; p=0.04); in PsA, obese patients were more likely to discontinue secukinumab (log-rank=5.25; p=0.021). The multivariable Cox-regression showed that arthritis was independently associated with a higher risk of secukinumab discontinuation (HR 2.43; 95%CI:1.06-5.55, p=0.035) after adjusting for age, sex, gender, BMI, therapy line and PsO severity at baseline.

Conclusions

Our data confirmed a good response to secukinumab in both PsO and PsA patients. However, presence of arthritis might affect drug survival.

Background and Aims

An ACR/EULAR task force released new criteria in 2013 to classify patients with systemic sclerosis (SSc). This study evaluates the diagnostic performance of these criteria in a multidisciplinary care setting.

Methods

Patients with an active follow-up in a Systemic Autoimmune Diseases Unit with clinical diagnosis of SSc (SSc-cases) were matched by age and gender with consecutive patients referred to a capillaroscopy clinic (controls). The classification criteria were tested on discrimination and diagnostic accuracy between both groups of patients. Receiver operating characteristic (ROC) curve and the area under the curve (AUC) was calculated for the global score to define the best cut off to classify the SSc patients.

Results

130 patients with SSc and 130 matched-controls were included in this analysis, 90% women, with a mean age of 61.5. Main diagnosis for the control group were primary Raynaud´s phenomenon (34.6%), undifferentiated connective tissue disease (13.1%), and mixed connective tissue disease (9.2%). The 92% and 8% of patients in the SSc-cases and control groups met the 2013 ACR/ EULAR SSc classification criteria respectively. Sensitivity and specificity of the criteria were 81.5% and 93.7%, respectively. The best cut offs for the score were 8 and 9, and the AUC (95%CI) was 0.962 (0.939-0.985). The individual items with a better discriminatory capacity were abnormal capillaroscopy, telangiectasia and anticentromere antibody positivity.

Conclusions

The ACR/EULAR 2013 criteria showed good diagnostic properties in this cohort reflecting daily practice. Individual items showing the highest discriminatory capacity were abnormal capillaroscopy, telangiectasia and anticentromere antibody positivity.