Caffeine improves systemic lupus erythematosus endothelial dysfunction by promoting endothelial progenitor cells survival.

OBJECTIVE: We studied the role of caffeine intake on endothelial function in SLE by assessing its effect on circulating endothelial progenitor cells (EPCs) both ex vivo in SLE patients and in vitro in healthy donors (HD) treated with SLE sera. METHODS: We enrolled SLE patients without traditional cardiovascular risks factors. Caffeine intake was evaluated with a 7-day food frequency questionnaire. EPCs percentage was assessed by flow cytometry analysis and, subsequently, EPCs pooled from six HD were co-cultured with caffeine with and without SLE sera. After 7 days, we evaluated cells' morphology and ability to form colonies, the percentage of apoptotic cells by flow cytometry analysis and the levels of autophagy and apoptotic markers by western blot. Finally, we performed a western blot analysis to assess the A2AR/SIRT3/AMPK pathway. RESULTS: We enrolled 31 SLE patients, and observed a positive correlation between caffeine intake and circulating EPCs percentage. HD EPCs treated with SLE sera and caffeine showed an improvement in morphology and in number of EPCs colony-forming units in comparison with those incubated without caffeine. Caffeine was able to restore autophagy and apoptotic markers in HD EPCs as before SLE sera treatment. Finally, caffeine treatment was able to significantly reduce A2AR levels, leading to an increase in protein levels of SIRT3 and subsequently AMPK phosphorylation. CONCLUSIONS: Caffeine intake positively correlated with the percentage of circulating EPCs in SLE patients; moreover, caffeine in vitro treatment was able to improve EPC survival and vitality through the inhibition of apoptosis and the promotion of autophagy via A2AR/SIRT3/AMPK pathway.

Clinical, histologic, and immunologic signatures of Small Fiber Neuropathy in Systemic Lupus Erythematosus.

BACKGROUND AND OBJECTIVES: Systemic Lupus Erythematosus (SLE) often causes damage to small nerve fibers, leading to distressing painful and autonomic symptoms. Despite this, Small Fiber Neuropathy (SFN) remains an underrecognized complication for SLE patients. In this cross-sectional study, we aimed to assess SFN in patients with SLE and to explore its correlations with immunologic disease features and clinical manifestations. METHODS: We recruited 50 SLE patients (1 male to 12.5 females, aged 20-80 years) reporting painful disturbances. We conducted a comprehensive clinical and neurophysiological evaluation, using Nerve Conduction Studies and Quantitative Sensory Testing. Additionally, we carried out an extensive laboratory assessment of disease-related serological parameters. We also performed a thorough skin biopsy analysis, investigating somatic and autonomic innervation while detecting complement and inflammatory cell infiltrates within the skin. RESULTS: Out of 50 patients, 19 were diagnosed with SFN, primarily characterized by a non-length-dependent distribution; 7 had a mixed neuropathy, with both large and small fiber involvement. Patients with SFN were younger than patients with a mixed neuropathy (p = .0143); furthermore, they were more likely to have a history of hypocomplementemia (p = .0058) and to be treated with cyclosporine A (p = .0053) compared to patients without neuropathy. However, there were no significant differences in painful and autonomic symptoms between patients with and without SFN. DISCUSSION: This study highlights the relevant frequency of SFN with a non-length-dependent distribution among SLE patients experiencing painful symptoms. Indeed, SFN emerges as an early manifestation of SLE-related neuropathy and is closely associated with hypocomplementemia, suggesting a potential pathogenic role of the complement system. Moreover, SFN may be influenced by disease-modifying therapies. However, the precise role of SFN in shaping painful and autonomic symptoms in patients with SLE remains to be fully elucidated.

Hepatitis E Virus Infection in Patients with Systemic and Cutaneous Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by a multifactorial etiology in which genetic and environmental factors interplay. An exclusively cutaneous condition has been described and defined as cutaneous lupus erythematosus (CLE). In Italy, a nationwide blood donor survey found an overall HEV prevalence of 8.7%, with an interregional variation from 2.2% to 22.8%. In this study, we aimed to estimate HEV seroprevalence in a cohort of patients affected by SLE and CLE attending the Lupus Clinic, Sapienza University of Rome. Serum samples were tested for anti-HEV immunoglobulin Ig G and M antibodies using commercial enzyme-linked immunosorbent assay (ELISA) kits. Statistical analysis was performed. In total, 138 patients were enrolled, 92 (67%) affected by SLE and 46 by CLE. The prevalence of HEV infection was 23.9% in the CLE group and 7.6% in the SLE group. The anti-HEV+ prevalence was significantly more frequent in CLE. Some mechanisms may be linked to increased susceptibility to HEV such as a molecular mimicry associated with the CLE condition or with the skin compartment/skin self-antigens, as well as the involvement of the genetic background. Regarding the possible risk factors, no association was found, although, of note, the odds of HEV+ relative to contact with animals and to eating raw seafood were strongly higher than the unit in the CLE group.

Fever in systemic lupus erythematosus: associated clinical features and genetic factors.

OBJECTIVES: Fever has been recently included in the new 2019 EULAR/ACR classification criteria for systemic lupus erythematosus (SLE). Thus, we investigated the possible association of fever with other clinical disease manifestations. Then, we analysed a panel of 30 SNPs to verify their possible contribution to the pathogenesis of this constitutional symptom. METHODS: In this retrospective study we collected clinical/laboratory features in a SLE cohort, including the occurrence of fever (body temperature >37.5°C, excluding infective aetiology). A phenotype-genotype correlation analysis was carried out. RESULTS: We evaluated 167 patients (M/F 12/155, median age at the disease diagnosis 30 years, IQR 17; median disease duration 240 months, IQR 156). Seventy patients (41.9%) reported fever, significantly associated with: serositis and haematological manifestations (p=0.02 and p=0.00001, respectively). A significant association between fever and leukopenia (p=0.003), haemolytic anaemia (p=0.04), and thrombocytopenia (p=0.04) was observed. In addition, significantly higher median SLICC Damage Index (SDI) values were observed in patients with fever in comparison with those without [2 (IQR 3) vs. 1 (IQR 2); p=0.005]. The genotype/phenotype analysis showed an association between fever and the rs13361189 of Immunity Related GTPase M (IRGM) gene (p=0.003; OR 3.89, CI 1.16-13.03), confirmed also in multivariate logistic regression analysis (p=0.028, B=1.39). CONCLUSIONS: The association between IRGM rs13361189 polymorphism and the occurrence of inflammatory fever, could provide new insights into the role of genetic background in the pathogenesis of this SLE-related feature.

Erosive arthritis in systemic lupus erythematosus: application of cluster analysis.

OBJECTIVES: In the present study, we applied cluster analysis (CA) in SLE patients with joint involvement to identify which disease subset most commonly develops erosive damage. METHODS: We collected clinical and laboratory data of SLE patients with a clinical history of joint involvement (arthritis/arthralgia). Ultrasonographic assessment was performed at level of MCPs and PIPs joints, to identify erosive arthritis, defined as the presence of erosions in at least one joint. Moreover, we detected RF, ACPA anti-CarP, and Dkk1 serum levels. We applied an unsupervised hierarchical CA to identify the aggregation of patients into different subgroups sharing common characteristics in terms of clinical and laboratory phenotypes. RESULTS: CA included 112 SLE patients (M/F 6/106; median age 45 years, IQR 17; median disease duration 96 months, IQR 165). Arthritis was observed in 82 patients (73.2%) and inflammatory arthralgia in 30 (26.8%). US-detected erosive arthritis was observed in 29 patients (25.9%). CA on clinical and laboratory features allowed the identification of four main clusters: in particular erosive arthritis was located in a cluster including renal and neuropsychiatric involvement, serositis, positivity for ACPA, anti-Carp, anti-Sm, anti-RNP, detectable levels of Dkk1. CONCLUSIONS: The application of CA made it possible to better characterise SLE phenotype including erosive arthritis. In particular, feature-driven CA leads to the identification of a more aggressive disease, due to a common pathogenic mechanism.

The role of musculoskeletal ultrasound in predicting the response to JAK inhibitors: results from a monocentric cohort.

OBJECTIVES: In this longitudinal study, we assessed the role of musculoskeletal ultrasound (US) in predicting the efficacy of JAK inhibitors (JAKi) in rheumatoid arthritis (RA) patients. METHODS: We enrolled RA patients starting baricitinib or tofacitinib. All patients were evaluated at baseline and after 4, 12, 24, 48 weeks. Disease activity was calculated by Disease Activity Score 28 (DAS28CRP); US examination in 22 joints (I-V MCPs and PIPs, wrists) aimed at evaluating inflammatory features (synovial effusion and hypertrophy, power Doppler-PD), scored through a semi-quantitative scale (0-3). The total US (0-198) and PD (0-66) scores were calculated. We scanned bilateral flexor (I-V fingers of hands) and extensor compartments (1-6) tendons: tenosynovitis was scored as absent/present (0/1), resulting in a total score ranging from 0 to 22. RESULTS: We studied 102 patients (M/F 15/87; median age 59.2 years, IQR 17.75; median disease duration 144 months, IQR 126), 61 treated with baricitinib and 41 with tofacitinib. At baseline, the median total US score was 18 (IQR 19) and the median PD score 2 (4). We observed a significant reduction in both total and PD US scores at all time-points (p<0.0001). At baseline, 75.4% of patients showed tenosynovitis involving at least one tendon, with a median score of 2 (IQR 3.5) significantly decreasing after 24 weeks (p=0.02). At multivariate analysis, PD and tenosynovitis score significantly correlated with changes in DAS28CRP. CONCLUSIONS: The present study confirmed the early efficacy of JAKi in RA patients by using US evaluation. Furthermore, we found that power Doppler and tenosynovitis scores could play a predictive role in response to treatment.

Hepatitis B and C virus infection in patients with Systemic and Cutaneous Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by a multifactorial etiology. The primary aim of this study was to estimate HCV and HBV infection prevalence in a cohort of SLE and Cutaneous Lupus Erythematosus (CLE). We assessed the frequency of these infections in our cohort and the possible associations with disease clinical/laboratory features and disease activity status. The prevalence of chronic HBV infection was 2.2% in the CLE group, while no HBsAg positive patients were identified in the SLE group. Conversely, the prevalence of anti-HCV positive was 2.2% in the SLE group while no anti-HCV positive patients were identified in the CLE group. We found no significant association between anti-HBc positive status and clinical manifestations or disease activity status in either group of patients. Hemodialysis resulted significantly associated with anti-HBc positivity in SLE. In the present study, we found HBsAg positivity in CLE patients but not in the Systemic form (SLE); conversely, a similar prevalence of anti-HBc antibodies in both groups was observed. A possible protective role exerted by SLE in HBV infection may be hypothesized. A higher frequency of HCV infection in SLE compared to CLE suggests a possible involvement of HCV in some SLE-related clinical and immunological features.

Pregnancy outcome in systemic lupus erythematosus patients: a monocentric cohort analysis.

OBJECTIVE: SLE is an autoimmune disease, mainly affecting women of childbearing age, with possible impact on pregnancy. In this study, we evaluated pregnancy outcomes in all pregnant patients affected by SLE, followed in the context of a rheumatology/gynaecology multi-disciplinary team. METHODS: Since 2008, we evaluated 70 consecutive pregnancies occurring in 50 SLE patients referring to the Lupus Clinic of Sapienza University of Rome; as controls we evaluated 100 consecutive pregnancies in 100 women without autoimmune diseases. RESULTS: By comparing SLE patients and controls, we did not find differences in terms of pregnancy outcomes, except for the occurrence of small for gestational age, which was significantly higher in the SLE group (22.8% vs 11%, P =0.003). Small for gestational age was associated with the positivity for anti-dsDNA, anti-Sm and anti-RNP (P =0.009, P =0.02, P =0.002, respectively). A disease flare was reported in 28 pregnancies (40%) and in 31 puerperium periods (44.3%). Flare during pregnancy was associated with anti-SSA (P =0.02), while puerperium relapse with previous MMF treatment (P =0.01) and haematological flare during pregnancy (P =0.03). CONCLUSION: The present study confirms how pre-gestational counselling and a multi-disciplinary approach could result in positive pregnancy outcomes for SLE patients. The high percentage of disease relapse justifies even more the need for multi-disciplinary management.

Breastfeeding in women affected by systemic lupus erythematosus: Rate, duration and associated factors.

OBJECTIVE: Breastfeeding is a crucial moment for both mothers and child, providing a beneficial effect on child survival, nutrition, development and on maternal health. Despite the prevalent involvement of childbearing women in systemic lupus erythematosus (SLE), breastfeeding is still a neglected topic. The objective of this study was to evaluate breastfeeding frequency, duration and associated factors in SLE women. METHODS: We consecutively enrolled SLE pregnant women reporting demographic, clinical, serological, gynaecological and obstetric data. Breastfeeding experience was evaluated by using a specific questionnaire. Disease activity was assessed before and during pregnancy as well as during postpartum. RESULTS: A total of 57 pregnancies in 43 SLE women were included in the present study. In almost all the pregnancies, mothers planned to breastfeed their child (96.5%) and forty-one (71.9%) actually did breastfeed. The median time of breastfeeding was 3 months (IQR 7). Non-breastfeeding women showed a more frequent caesarean section (p = 0.0001), IUGR occurrence (p = 0.004) and disease relapse (p = 0.0001) after pregnancy. When comparing patients according with breastfeeding duration (cut-off 6 months), we found a significant more frequent smoking habitus (p = 0.02), caesarean section (p = 0.009), and joint involvement during postpartum (p = 0.0001) in women breastfeeding for less than or equal to 6 months, together with higher median BMI (p = 0.0001). Moreover, breastfeeding duration was positively associated with disease duration and hydroxychloroquine (HCQ) treatment during disease history, pregnancy and postpartum. CONCLUSIONS: SLE women didn't show lower breastfeeding rate in comparison with general population but they presented higher prevalence of early discontinuation within three months. Early interruption was positively associated with smoking, BMI, joint involvement; meanwhile disease duration and HCQ treatment during postpartum were positively associated with a longer breastfeeding duration.

Erosive arthritis in systemic lupus erythematosus: not only Rhupus.

Systemic lupus erythematosus (SLE)-related arthritis has been traditionally defined as non-erosive and is therefore considered a minor manifestation requiring a mild treatment. However, the concept of non-erosive arthritis in SLE has been challenged with the advent of sensitive imaging techniques, such as high-resolution ultrasound with power Doppler or magnetic resonance. The application of these new imaging tools has demonstrated that up to 40% of SLE patients with joint involvement can develop erosive damage. Thus, this more aggressive phenotype can be identified not only in patients overlapping with rheumatoid arthritis (RA). This issue has been considered for the first time in the classification criteria proposed by Systemic Lupus International Collaborating Clinics in 2012, in which the old definition of "non-erosive arthritis" was replaced with either synovitis or tenderness in two or more joints with morning stiffness, suggesting the possible presence of an erosive phenotype. Accordingly, the 2019 EULAR/ACR's SLE recommendations advise treatment with immunosuppressant or biological drugs for patients with RA-like moderate arthritis. As a result, several studies have investigated the presence of biomarkers associated with SLE erosive damage. A relevant role seems to be played by the autoantibodies directed against post-translational modified proteins: above all, a significant association has been observed with antibodies directed against citrullinated and carbamylated proteins. Conversely, the rheumatoid factor was not associated with this more aggressive SLE-related arthritis. Nonetheless, some pro-inflammatory factors have been associated with erosive damage in SLE patients. These results suggest new pathogenic mechanisms underlining erosive arthritis, only partially shared with RA. Hence, in the present narrative review, we summarized available data about erosive arthritis in SLE patients, in the light of its impact on therapeutic decisions.

Joint involvement influences quality of life in systemic lupus erythematosus patients.

INTRODUCTION: Joint involvement represents the major determinant in quality of life (QoL)in Systemic Lupus Erhytematosus (SLE) patients. However, QoLhas been generally evaluated by non-specific questionnaires. We evaluated the relationship between SLE musculoskeletal manifestations and QoL, assessed by LupusQoL. METHODS: Patients with joint involvement (group A) were compared with those without this feature (group B). Disease activity was assessed by SLEDAI-2k in the whole population, while DAS28 and swollen to tender ratio were applied to assess joint activity. LupusQoL was administered to all the patients. RESULTS: Group A included 110 patients [M/F 8/102; median age 49 years (IQR 13), median disease duration 156 months (IQR 216)], group B 58 [M/F 11/47; median age 40 years (IQR 15), median disease duration 84 months (IQR 108)].We found significanlty lower values in all the LupusQoL domains except for one (burden to others) in group A in comparison with group B. A significant correlation between DAS28 values and all the LupusQoL domains in group A was found; only three domains correlated with SLEDAI-2k. CONCLUSIONS: SLE-related joint involvement significantly influences disease-specific QoL. DAS28 better correlated with LupusQoL domains in comparison with SLEDAI-2k, confirming the need for specific musculoskeletal activity indices.

Perceived Disease Activity in Rheumatoid Arthritis: When the Physician's Gender Matters.

BACKGROUND: In rheumatoid arthritis (RA), females usually have a worse prognosis. To date, the influence of physician gender in the evaluation of RA activity is still largely unknown. OBJECTIVES: To investigate the discrepancy in RA disease activity assessment between male and female physicians and to compare patient and evaluator perception of disease activity and global health (GH) status. METHODS: One female and one male rheumatologist evaluated 154 RA patients recording tender and swollen joint count, GH, evaluator global assessment (EGA), and patient global assessment (PGA) disease activity. A third rheumatologist calculated DAS28, CDAI, and SDAI. Difference was evaluated by Wilcoxon test. Physician-patient agreement was assessed by intraclass correlation coefficient. RESULTS: GH, PGA, and DAS28 were higher when recorded by the female examiner. Male EGA was higher than female. Among male patients, PGA was higher when collected by the female examiner. The probability of being judged as having an active disease did not rely on physician gender. The agreement with the physician's evaluation of disease activity was high. PGA values were higher than EGA in both examiners. The physician-patient agreement was moderate for the male examiner and good for the female. The female physician had a higher agreement with both genders. CONCLUSIONS: Subjective measure of disease activity differs between female and male rheumatologists, contributing to a different evaluation of disease activity. Patients have a higher perception of disease activity compared to physicians. The stronger agreement between female physicians and patients may be related to a more emphatic setting established by the female physician.

Premature ovarian failure in patients affected by systemic lupus erythematosus: a cross-sectional study.

OBJECTIVES: We evaluated age at natural menopause and the prevalence of premature ovarian failure (POF) in a monocentric Caucasian cohort of patients with systemic lupus erythematosus (SLE). METHODS: In this cross-sectional study, we enrolled women affected by SLE compared with healthy controls (HC) to investigate data about natural menopause (amenorrhoea for at least 12 months at ≥40 years) and POF (amenorrhoea for at least 12 months at <40 years). RESULTS: We enrolled 196 SLE (median age 47.0 years, IQR 16.7; median disease duration 132 months, IQR 180) and 90 HC (median age 49.9 years, IQR 15.0). Ninety-four SLE (48.0%) and 26 HC (23.4%) were menopausal: median age at onset was significantly lower in SLE than HC (47 years, IQR 8.0 vs. 50.5 years, IQR 4; p=0.0001). POF was registered in 17% of the SLE, and in none of the HC (p<0.0001). POF was significantly associated with anti-Sm (p=0.0004), anti-RNP (p=0.02), anti-cardiolipin (p=0.0008), lupus anticoagulant (p=0.0002), treatment with cyclophosphamide (p=0.0001), azathioprine (p=0.0001), mycophenolate mofetil (p=0.0001), cyclosporine A (p=0.007). CONCLUSIONS: SLE patients develop menopause at a younger age; moreover, a higher POF frequency was observed in SLE patients in comparison with HC. POF is associated with specific SLE-related autoantibodies and the use of immunosuppressant drugs, in particular cyclophosphamide.

Efficacy of Burosumab Every 2 Weeks in an Adult with X-Linked Hypophosphatemia: Should We Learn from Children?

X-linked hypophosphatemia is a genetic condition that leads to fibroblast-growth-factor 23 (FGF23) increase, causing phosphate renal wasting. Since 2018, burosumab, an anti-FGF23 antibody, has been used for this disease with different dosage in children and adults. We report the case of burosumab administration every 2 weeks, as usually done in children. We retrospectively evaluated parathormone (PTH), alkaline phosphatase, serum phosphate, tubular reabsorption of phosphate (TRP), and 25OH vitamin D every 2 weeks in a 29-year-old man with nephrocalcinosis and tertiary hyperparathyroidism who did not respond to standard treatment with burosumab nor to maximum dosage and was treated with burosumab 90 mg every 2 weeks. His serum phosphate and TRP increased with this regimen compared with 4 weeks frequency (respectively 1.74 ± 0.26 mg/dL vs. 2.3 ± 0.19 mg/dL [p 0.0004] and 71.3% ± 4.8% vs. 83.9% ± 7.9% [p 0.01]) with decrease in PTH (183 ± 24.7 pg/mL vs. 109 ± 12.2 pg/mL [p 0.04]). Burosumab may be a good choice in adult patients with X-linked hypophosphatemia; new data are needed regarding the increase in dosage and/or frequency of administration as usually done in children, to achieve disease control.

Evaluation of Renal Function and Scars in Children With Primary Vesicoureteral Reflux.

OBJECTIVE: To evaluate growth, glomerular and tubular function, renal damage, scars in children affected by primary VUR. METHODS: We retrospectively evaluated the clinical records of our Unit from January 2006 to September 2020. For each patient we evaluated growth, laboratoristic and scintigraphic glomerular and tubular function, renal damage and collective system urodynamics at baseline and at the last visit. RESULTS: We enrolled 41 patients affected by primary VUR and treated with continuous antibiotic prophylaxis. Glomerular function and urodynamics did not change over time. EFNa directly correlated with weight (r 0.44 P .004) and TRP inversely correlated with severity of reflux (r -0.32, P .04). Female sex was associated to nephrolithiasis (OR 17.0, P .02) and proteinuria (at T0 OR 5.8 P .03 at T1 OR 5.8, P .03). Daily proteinuria increased with age (r 0.66, P <.0001 at T0 and r 0.44 P .004 at T1) while protein-to-creatinine ratio decreased. Renal scars at T0 inversely correlated with glomerular and tubular function at T1 but they did not correlate with severity or laterality of reflux. CONCLUSION: Even if renal function remains stable through years, it is critical to identify the subjects with significant congenital renal damage.

Development of Systemic Autoimmune Diseases in Healthy Subjects Persistently Positive for Antiphospholipid Antibodies: Long-Term Follow-Up Study.

We longitudinally followed a single-center cohort of anti-phospholipid (aPL) positive healthy subjects to evaluate the evolution to systemic autoimmune diseases (sAD) and to describe clinical and serological associated features. Since 2010, we have consecutively screened healthy subjects who were positive, in at least two consecutive determinations, for one or more aPL [anti-Cardiolipin (aCL) IgM/IgG, anti-Beta2Glycoprotein I (aB2GPI) IgM/IgG, Lupus Anticoagulant (LA)]. All subjects were evaluated every six months, or in accordance with the patient's clinical course, in order to record the development of clinical and laboratory features suggestive for sAD. Ninety-five subjects [M/F 20/75, median age at first determination 46 years, Interquartile Range (IQR) 19] were enrolled. Thirty-three subjects (34.7%) were positive for only one aPL [15 (15.8%) for aCL, 15 (15.8%) for LA, and 5 (5.3%) for aB2GPI]; 37 (38.9%) had double positivity [32 (33.6%) for aCL and aB2GPI; 5 (5.3%) for aCL and LA], 23 (24.2%) had triple positivity. We prospectively followed up our cohort for a median period of 72 months (IQR 84). During a total follow-up of 7692 person-months, we found an absolute risk for sAD development equal to 1.8%. Specifically, 14 (14.7%) patients developed a sAD: in four patients (4.2%), after developing a thrombotic event, an antiphospholipid syndrome was diagnosed, 7 (7.4%) patients developed an Undifferentiated Connective Tissue Disease after a median period of 76 months (IQR 75.5), and lastly, three (3.1%) patients could be classified as affected by Systemic Lupus Erythematosus according to the ACR/EULAR 2019 criteria. The presence of triple positivity status resulted in being significantly associated with the progression to sAD (p-value = 0.03). In conclusion, we observed the development of sAD in almost 15% of aPL positive subjects. Triple positivity was significantly associated with this progression, suggesting a possible role as biomarker for this condition. Thus, our results could suggest the need for periodic follow-up for such patients to assess early diagnosis and treatment.

The Impacts of the Clinical and Genetic Factors on Chronic Damage in Caucasian Systemic Lupus Erythematosus Patients.

Objective: The purpose of this study was to determine the distribution of organ damage in a cohort of systemic lupus erythematosus (SLE) patients and to evaluate the roles of clinical and genetic factors in determining the development of chronic damage. Methods: Organ damage was assessed by the SLICC Damage Index (SDI). We analyzed a panel of 17 single-nucleotide polymorphism (SNPs) of genes already associated with SLE, and we performed a phenotype−genotype correlation analysis by evaluating specific domains of the SDI. Results: Among 175 Caucasian SLE patients, 105 (60%) exhibited damage (SDI ≥1), with a median value of 1.0 (IQR 3.0). The musculoskeletal (26.2%), neuropsychiatric (24.6%) and ocular domains (20.6%) were involved most frequently. The presence of damage was associated with higher age, longer disease duration, neuropsychiatric (NP) manifestations, anti-phospholipid syndrome and the positivity of anti-dsDNA. Concerning therapies, cyclophosphamide, mycophenolate mofetil and glucocorticoids were associated with the development of damage. The genotype−phenotype correlation analysis showed an association between renal damage, identified in 6.9% of patients, and rs2205960 of TNFSF4 (p = 0.001; OR 17.0). This SNP was significantly associated with end-stage renal disease (p = 0.018, OR 9.68) and estimated GFR < 50% (p = 0.025, OR 1.06). The rs1463335 of MIR1279 gene was associated with the development of NP damage (p = 0.029; OR 2.783). The multivariate logistic regression analysis confirmed the associations between TNFSF4 rs2205960 SNP and renal damage (p = 0.027, B = 2.47) and between NP damage and rs1463335 of MIR1279 gene (p = 0.014, B = 1.29). Conclusions: Our study could provide new insights into the role of genetic background in the development of renal and NP damage.

Molecular Characterization of Hepatitis B Virus Infection in a Patient with Cutaneous Lupus Erythematosus.

Hepatitis B virus (HBV) infection is a serious global health problem. Patients with autoimmune diseases, such as Lupus Erythematosus, are exposed to a higher risk of acquiring infections. In this study, a molecular characterization, genomic investigation of the Hepatitis B virus, polymerase (P) and surface (S) genes, from a patient affected by Cutaneous Lupus Erythematosus (CLE), was presented. Viral DNA was extracted from 200 µL of serum, and the HBV-DNA was amplified by real-time polymerase chain reaction (PCR) with the Platinum Taq DNA Polymerase. The PCR products were purified and sequencing reactions were performed. A phylogenetic analysis was performed through maximum likelihood and Bayesian approaches. The HBV CLE isolate was classified as sub-genotype D3 and related to other Italian HBV D3 genomes, and some from foreign countries. No drug resistant mutations were identified. One mutation (a.a. 168 M) was located in the last part of the major hydrophilic region (MHR) of the surface antigen (HBsAg). Moreover, three sites (351G, 526Y, 578C) in the polymerase were exclusively present in the CLE patient. The mutations identified exclusively in the HBsAg of our CLE patient may have been selected because of the Lupus autoantibodies, which are characteristic in the Lupus autoimmune disease, using a possible molecular mimicry mechanism.

Single-centre retrospective analysis of the best timing for the QTc interval length assessment in neonates.

Objective: To evaluate the best timing for ECG screening in order to diagnose long QT syndrome and lower, at the same time, the false positives. Design: We retrospectively evaluated the corrected QT (QTc) interval in the clinical reports of the ECG screening performed, as per internal protocol. Setting: An outpatient setting in our Unit of Neonatology and Pediatrics, Santa Maria Goretti Hospital in Latina, Italy. Patients: We enrolled 3467 healthy neonates between 14 and 30 days of life. Interventions: The newborns with abnormal QTc interval were invited to subsequent revaluation every 21 days, until normalisation or necessity to refer to a tertiary paediatric cardiology centre. Main outcome measures: Difference in QTc according to patients' characteristics and number of false positives at second ECG evaluation. Results: At first evaluation, 249 (7.2%) newborns had prolonged QTc. We did not find any significant difference in the QTc length according to gestational age (p=0.40) and birth weight (p=0.81). As expected, girls had longer QTc than boys (p=0.01). Only 11 out of 240 (4.6%) and 1 out of 238 infants (0.4%) had persistently prolonged QTc at second and third ECG evaluation, respectively. The QTc decreased significantly at second (p<0.0001) and third evaluation (p=0.0035). Conclusions: In our study, we showed that a single screening performed in healthy infants after 60 days of life could reduce the risk of false positives, with a beneficial impact on public national health system and the chance to start early therapy in case of long QT syndrome.

Five-years drug survival of mycophenolate mofetil therapy in patients with systemic lupus erythematosus: Comparison between renal and non-renal involvement.

OBJECTIVE: The EULAR recommendations underline the use of MMF for Lupus Nephritis (LN) but also for the treatment of moderate/severe non-renal manifestations (NLN). This study aims at evaluating the 5-years drug retention rate (DRR) of MMF in a SLE cohort in a real-life scenario. Secondly, we investigated the MMF influence to control chronic damage progression. METHODS: We performed a longitudinal study including all the SLE patients starting MMF in our Lupus Clinic (from 2008 to 2020). The DRR was estimated using the Kaplan-Meier method. RESULTS: We evaluated 162 SLE patients (M/F 22/140). The most frequent indications for prescribing MMF were LN (101 patients, 62.3%) and musculoskeletal manifestations (39, 24.1%) followed by NPSLE (10, 6.2%) and other manifestations (12, 7.4%). We registered a median treatment duration of 30 months (IQR 55). At 60 months follow-up we observed a DRR of 61.1% for LN patients, which was similar to that registered for patients without renal involvement (60.5%). The DRR was higher in the subgroup of patients with joint involvement (75.4%, P non-significant). During the overall observation period, 92 patients (59.2%) discontinued MMF. The main cause of withdrawal was the achievement of remission, observed in 20 patients (21.7%). Moreover, MMF resulted able to control chronic damage progression, as demonstrated by the lack of significant increase in the median SDI values (baseline: 0.6, IQR 1; last: 0.93, IQR 1). CONCLUSIONS: Our finding suggested that MMF is a safe and effective drug for SLE manifestations other than LN, especially for joint involvement. Moreover, it was able to control the chronic damage progression.