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To determine whether any of the HLA-A*, HLA-B* and HLA-DR* alleles in seropositive rheumatoid arthritis (RA) can be associated with the extreme serum levels of rheumatoid factor (RF) and cyclic citrullinated peptide antibodies (anti-CCP). This was a retrospective cross-sectional study of adult patients. Demographic data, HLA typing data and RF and anti-CCP levels were collected and analysed. HLA-A*02, HLA-B*44 and HLA-DRB1*04 were more prevalent in patients from the RA cohort compared to healthy controls. Intra-cohort analysis revealed that HLA-B*44 had an increased frequency of a twenty-fold increase in anti-CCP (P = 0.033) and HLA-A*03 had a borderline (P = 0.063) frequency. HLA-A*03 was more frequent in the groups with >3-fold and >10-fold anti-CCP levels, while HLA-DRB1*04 was of borderline significance at >3-fold anti-CCP increase (P = 0.053). HLA-B*08 showed a lower frequency of 3-, 10- and 20-fold increase in anti-CCP serum levels. Carriers of B*44 (OR = 5.58; P = 0.030), DRB1*04 (OR = 3.89; P = 0.027) or A*03 (OR = 2.71; P = 0.023) were statistically significantly more likely to have a 20-fold increase in anti-CCP levels over the diagnostic threshold. None of the alleles increased the likelihood of having high or extreme RF levels. HLA-B*44 is associated with a twenty-fold increase in anti-CCP serum levels. HLA-A*03 and HLA-DRB1*04 have a positive trend towards a twenty-fold increase in anti-CCP levels. Earlier aggressive therapy in these patients can prevent such an extreme increase in antibody levels.

Background and Objective: The most prominent feature of systemic sclerosis (SSc), besides vasculopathy and autoimmune disorders, is excessive fibrosis. Serotonin affects hemostasis and can induce vasoconstriction, which is presumed to be one of the pathophysiological patterns in SSc that leads to fibrosis. Our aim was to explore the possible association of serotonin with some of the clinical features of SSc in our cohort of patients. Materials and Methods: We measured serotonin levels in sera of 29 female SSc patients. Patients were 41–79 years old, their average disease duration was 9 years. Serotonin values were analyzed in correlation with clinical and laboratory parameters, such as modified Rodnan skin score (mRSS), digital ulcers (DU), and spirometry parameters-forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), and lung diffusion capacity of carbon monoxide (DLCO). Statistical analyses were performed using statistical software Statistica. Results: We found correlation of serotonin level with mRSS (r = 0.388, p = 0.038). The highest values of serotonin were documented in patients with refractory DU, but this was not statistically significant. We also found a negative correlation between serotonin and FVC (r = −0.397), although it did not reach the level of significance (p = 0.114). Conclusions: Our study suggests that levels of serum serotonin could affect the course of skin fibrosis and partially restrictive pulmonary dysfunction in patients with SSc. We assume that serotonin might have influence on several features of SSc, but more studies are needed to reveal those relations.

The aim of this study was to develop a Croatian Delphi-based expert consensus for screening interstitial lung disease (ILD) associated with connective tissue disease (CTD). A systematic literature review was conducted on risk factors for the development of ILD, prevalence and incidence of ILD, diagnostic and screening methods for ILD, and prognosis of ILD in idiopathic inflammatory myopathy (IIM), mixed connective tissue disease (MCTD), primary Sjögren’s syndrome (pSS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and systemic sclerosis (SSc) were performed. Based on the evidence found, experts developed questionnaires for screening and monitoring ILD in each CTD, which were provided via an online survey. Following the electronic survey, two screening algorithms were developed based on the consensus opinions. The detection strategy for ILD included high-resolution computed tomography (HRCT) in addition to pulmonary function testing for IIM, MCTD, and SSc. and pulmonary function testing for newly diagnosed pSS, RA and SLE. However, in patients with identified risk factors for ILD HRCT, these tests should also be performed. A screening strategy for early identification of patients with various CTD-ILD was first developed by a multidisciplinary team of rheumatologists, pulmonologists, and radiologists to identify early CTD patients at risk of ILD, a severe extra-articular manifestation of CTD.

ObjectiveThe aim of this pilot-study was to examine serum calprotectin levels (sCAL) in patients with SLE and determine possible association with disease activity and history of vascular events.Methods27 consecutive SLE patients from daily hospital and outpatient rheumatology clinic and 13 healthy volunteers underwent demographic data collection, sCAL assessment (ELISA Buhlmann sCAL diagnostic test), and disease activity assessment by SLEDAI-2K for SLE patients. Patients were divided into two groups, active disease and remission, taking SLEDAI-2K value of 6 as a cut-off, and defined patients who had recent vascular incidents associated with SLE.Results13 patients in active group (38.5% women, median age 50 (35–58), SLE duration 8.85±6.26 years, SLEDAI-2K 14 (7–21)) were compared to 14 patients in remission group (85,7% women, median age 39 (35–53), disease duration 5.21±2.78 years, SLEDAK-2K 3.5 (2–4)) and to 13 control subjects (76,9% women, median age 25 (24–26)). Significantly higher occurrence of neuropsychiatric disease (53.8% vs. 14.3%, P=0.032) and vascular manifestations (76.9% vs. 14.3%, P=0.001) was observed in active patients compared to those in remission. We haven’t observed the difference in occurrence of APS, serositis, dermatologic, constitutional, renal, or hematologic manifestations of SLE between groups. sCAL levels were higher in all patients compared to the control group (1.1 (0.53–1.8) μg/ml vs. 0.7 (0.38–1.1) μg/ml, P=0.02). Moreover, sCAL was higher in the active group compared to remission patients (1.6 (1.1–3.0) μg/ml vs. 0.8 (0.2–1.4) μg/ml, P= 0.02). Patients with a history of recent vascular events had greater sCAL respect other SLE patients (1.7 (1.15–3) μg/ml vs. 1.0 (0.225–1.375) μg/ml, P=0.015). There was a positive correlation between SLEDAI and sCAL in all patients (ρ=0.532, P=0.0043), particularly in active ones (ρ=0.673, P=0.0017). There was no correlation between SLEDAI and sCAL within inactive patients (ρ=0.0678, P=0.818).ConclusionsSLE patients, especially those with active disease, had higher sCAL compared to healthy subjects. We established a positive correlation between vascular manifestations of SLE and sCAL, but also between SLEDAI-2K and sCAL in patients with active disease. Our study was limited due to the small sample size. Further research should confirm these hypotheses on a larger number of subjects.AcknowledgementThe authors declare no conflict of interest. This research was funded by the University of Split, School of Medicine.

Objective: The genetic background of HLA-B*27 in spondyloarthritis is known, and the search for another gene with similar role is ongoing. We wanted to investigate clinical presentations of HLA-B*44 patients in rheumatology practice. Methods: A cross-sectional retrospective study of 303 HLA-B*44 adult patients from the outpatient rheumatology clinic from 5/2018-5/2024. Clinical phenotype, confirmed or excluded rheumatic diagnosis, therapy used, and data on HLA A, B, and DR alleles inherited with B*44 were analyzed. Results: A female predominance of 2.79:1 was noted. A total of 150 [49.5%] patients were referred due to peripheral joint pain, 77 [25.4%] due to combined spine and peripheral joint pain or spine alone (57 [18.8%]). A total of 19 [6.3%] patients had no symptoms of the musculoskeletal system. Statistically significant peripheral joint affection was proved in females but not in males (p = 0.04). A total of 121 [40%] patients from B*44 group had established rheumatic disease, with the rest being excluded or under observation. The most common working diagnoses were polyarthritis (32 [10.5%]) and mono-oligoarthritis (14 [4.6%]). A second allele in addition to HLA B*44 showed a similar frequency to the general population. Patients with HLA B*44/44 and B*27/44 genotypes were at the most risk for having definitive rheumatic disease (>60%). Conventional synthetic disease-modifying anti-rheumatic drugs (DMARDs) were used in 38.6% of patients, non-steroidal anti-inflammatory drugs were used in 31.6% of patients, biologic DMARDs were used in 8.9% of patients, and corticosteroids were used in 7.3% of patients. Conclusions: The most common presentation in HLA-B*44 patients is peripheral joint affection. Most patients with HLA-B*27/44 and B*44/44 genotypes had definitive rheumatic disease. B*44 homozygosity or B*27/44 might be risk factors for arthritis development.

Background: We aimed to investigate possible association between the HLA-B*35 allele and peripheral arthritis, tenosynovitis and enthesitis. Methods: Ultrasound of peripheral joints and tendons was performed in 72 HLA-B*35 positive patients with preliminary diagnosis of undifferentiated axial form of spondyloarthitis and joint and tendon pain. Patients with other known types of axial and peripheral spondyloarthritis were excluded as well as patients with other known types of arthritis. Results: Pathological changes were found in the joints of 33 (46%) patients and on the tendons in 13 (18%) patients. The most common ultrasound findings were joint effusion and synovial proliferation with positive power Doppler signal grade 1. The most common ultrasound finding in patients with painful tendons was tenosynovitis. A higher disease activity and an increased incidence of elevated CRP (≥5 mg/L) were more often observed in the group with positive ultrasound findings. Conclusion: In this study, we showed that the HLA-B*35 allele could be a potential risk factor for developing peripheral arthritis, but not for tenosynovits and enthesitis in patients with the undifferentiated axial form of spondyloarthritis. This result may influence the follow up of these patients, especially since it gives us an opportunity to consider the use of different types of DMARDs in the treatment of these patients.

We present a case of an immunocompromised systemic lupus erythematosus female patient admitted to our hospital for general impairment, monoparesis, and temporary cognitive disability. The case represented a significant diagnostic and therapeutic challenge primarily because of a wide range of differential diagnosis options (CNS lupus, ischemic cerebrovascular disease, viral meningoencephalitis, progressive multifocal leukoencephalopathy, limbic encephalitis, and acute disseminated encephalomyelitis—ADEM). Brain MRI findings were compatible with ADEM, and microbiological tests showed a cytomegalovirus infection (CMV) which is rarely associated with ADEM despite the increasing number of immunocompromised patients prone to symptomatic CMV reactivation. Our patient was treated with intravenous methylprednisolone, immunoglobulin (IVIG), along with antiviral therapy resulting in a favorable therapeutic effect. In conclusion, only a few described ADEM cases have been associated with CMV, and none of them, to the best of our knowledge, in an immunocompromised patient. In this case, a multidisciplinary approach and broad diagnostic considerations were decisive for successful treatment and outcome.

We examined the role of adipokines and pro-inflammatory cytokines in psoriatic arthritis-associated subclinical myocardial dysfunction, and the relationship between these variables and psoriatic arthritis (PsA) disease activity. Fifty-five PsA patients without cardiovascular risk factors and 25 controls underwent standard and speckle tracking echocardiography with global longitudinal strain (GLS) calculated. Standard anthropometric data and Disease Activity in Psoriatic arthritis (DAPSA) scores were recorded, with low disease activity defined as DAPSA ≤ 14 and moderate and high disease activity DAPSA > 14. Standard biochemical tests, adiponectin, resistin, leptin, tumor necrosis factor (TNF) alfa, interleukin 17 A (IL-17A), B lymphocyte chemoattractant (BLC), and monokine induced by intereferon gamma (MIG) were analyzed. Median age was 53.0 (46.0–61.0), median PsA duration 6.0 (4.0–13.0) years and median DAPSA score 25.5 (13.0–41.5). Lower GLS, tricuspid annular plane systolic excursion (TAPSE) and left ventricular ejection fraction (LVEF) were found in moderate and high PsA disease activity compared to low PsA disease activity and controls. PsA patients with GLS < 20 had higher body mass index (BMI), DAPSA score and uric acid levels, and lower adiponectin levels. Although patients with GLS < 20 had higher IL-17A levels, it was not statistically significant ( P  = 0.056). However, when we included healthy controls and analyzed differences based on a GLS cut-off of 20% in the entire population, the difference in IL-17A became statistically significant, 0.17 pg/mL (0.06–0.32) vs. 0.43 pg/mL (0.23–0.65), P  = 0.017. The association between DAPSA score and GLS and IL-17 remained significant in multivariate analysis. Moreover, the association between GLS and IL-17 and adiponectin was significant after adjustment for age and BMI. Patients with moderate and high PsA disease activity have reduced myocardial function, lower adiponectin, and higher IL-17A levels.

ObjectiveTo investigate possible association between sacroiliitis and HLA-B*35 positivity.MethodAfter excluding patients with axial spondyloarthritis and HLA-B*27 positivity, psoriasis inflammatory bowel disease, preceding infections, or juvenile type of spondyloarthritis, 110 patients were recruited with a diagnosis of undifferentiated axial spondyloarthritis. All of them had inflammatory back pain of short duration (3 months to 2 years) and 72 were HLA-B*35 positive. In order to determine if there is a possible association of sacroiliitis and HLA-B*35 positivity, all patients underwent MRI of sacroiliac joints.ResultsA statistically significant association between the detection of bone marrow edema at sacroiliac joints on MRI and HLA-B*35 positivity (χ2 = 6.25; p = 0.022) was found. A logistic regression analysis revealed that the presence of HLA-B*35 allele was associated with a 6 times greater chance of identifying bone marrow edema at sacroiliac joints on MRI (OR 6, 95% CI 1.3–27, p = 0.021). HLA-B*35 positivity was also associated with a 4.7 times greater chance of finding elevated CRP (OR 4.7, 95% CI 1–11.9, p = 0.047) and a 5 times greater chance of finding peripheral joint synovitis (OR 5, 95% CI 1.75–14.3, p = 0.003). HLA-B*35-positive patients had high disease activity (mean ± SD of Bath Ankylosing Spondylitis Disease Activity Index 6.1 ± 1.72 and Ankylosing Spondylitis Disease Activity Score C-reactive protein Index 3 ± 0.64) with a high degree of functional limitations (mean ± SD of Bath Ankylosing Spondylitis Functional Index 5.3 ± 2.16).ConclusionThe data clearly show the association between bone marrow edema on MRI at sacroiliac joints and HLA-B*35 allele in patients with undifferentiated spondyloarthritis. Further work is needed to understand how much this result may influence follow-up of these patients.Key Points• HLA-B*35 allele was associated with a 6 times greater chance of identifying bone marrow edema at sacroiliac joints on MRI in un-axSpa patients.• HLA-B*35 allele was also associated with a 4.7 times greater chance of finding elevated CRP and a 5 times greater chance of finding peripheral joint synovitis in un-axSpa patients.• HLA-B*35 allele could be a potential risk factor for developing sacroiliitis and axSpA.