Primary Sjögren's syndrome (pSS) is a complex disabling systemic autoimmune disorder. The hallmark of pSS is the T-cell-mediated hyperactivation of B-cells, evolving from asymptomatic conditions to systemic complications and lymphoma development. On tissue level, the typical feature is the lymphocytic infiltration of the salivary gland by B-, T-and antigen presenting cells, as mirrored by the diagnostic cornerstone role of minor salivary gland (MSG) biopsy. B-cells show multiple possible roles in disease pathogenesis, from autoantibody production, to antigen presentation, and cytokine production. B-cells hyperactivation is supported by genetic risk factors, T-cell dependent and independent mechanisms, and the presence of different pathogenic B-cell subsets must be reminded. Many aspects have been investigated in the last year regarding genetic and epigenetics, B-and T-cell role in pSS pathogenesis, their interaction with salivary gland epithelial cells (SGECs) and in their direct or indirect use as biomarkers and predictors of disease development, activity, and lymphomagenesis.In this review, following the others of this series, we will summarise the most recent literature on pSS pathogenesis and clinical features focusing in particular on new insights into pSS molecular stratification and therapeutic advances in the era of precision medicine.
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BackgroundGrowing evidence from in vitro and clinical studies have highlighted important similarities between severe COVID-19 and rapidly progressive interstitial lung diseases (ILD) occurring in systemic autoimmune disorders. These data supported the use of anti-rheumatic drugs, baricitinib and glucocorticoids, for the treatment of COVID-19 pneumonia.ObjectivesTo compare mortality rate and inflammatory response in critically ill COVID-19 patients treated with either a “rheumatologic approach” based on baricitinib plus pulse steroids (BPS) or with a “conventional approach” (Standard of Care, SoC).MethodsIn this retrospective study, we enrolled patients admitted to the Intensive Care Unit (ICU) with CT-proven SARS-CoV2 pneumonia, from September 2020 to April 2021. Demographic, laboratory, and clinical data were collected at the admission to ICU and after one week of treatment. SoC included dexamethasone 6 to 8 mg daily plus remdesivir (+/- antibiotics and hydroxychloroquine); BPS approach was based on baricitinib 4 mg daily for 10-14 days plus 6-methylprednisolone pulses (250-500 mg) for three consecutive days followed by rapid tapering. The primary endpoint was the intra-ICU mortality rate; the secondary endpoint was the change in inflammatory biomarkers at week 1 after treatment.ResultsWe enrolled a total of 210 consecutive patients with SARS-CoV2 pneumonia (male 61.4%, mean age 66.6 ± 10.9 years); 137/210 (male 59.8%, mean age 66.3 ± 11.9 years) were treated with SoC and 73/210 (male 64.3%, mean age 67.3 ± 8.8 years) with BPS.At admission in ICU, all patients presented lag time from the first symptom of SARS-CoV2 infection ≤ 10 days, laboratory biomarkers’ alterations suggestive of hyper-inflammatory response (CRP 10.8 ± 11.9 mg/dL, ferritin 1238 ± 1005 µg/L, fibrinogen 575 ± 173 mg/dL, LDH 385 ± 152 U/L) and severe respiratory failure, requiring non-invasive or invasive ventilatory support. Lung-CT pattern showed multiple and diffuse areas of ground glass opacities, septal thickening, and/or consolidation.No statistically significant differences were found between SoC and BPS groups in terms of demographic, laboratory, and clinical features at enrolment.59/210 (28.1%) patients died during ICU hospitalization (mean ICU length of stay 14.6 ± 9.6 days). Mortality rate in the BPS group (13/73, 17.8%) resulted significantly lower compared to that in the SoC group (46/137, 33.6%) (p= 0.016). Furthermore, patients in the BPS group had significantly lower levels of CRP (BPS=1.9 ± 2.8 vs SoC 6.1 ± 7.3, p<0.001) and fibrinogen (BPS=335 ± 108 vs SoC 453 ± 172, p<0.001) at one week after the start of treatment.ConclusionOur real-life experience, in an ICU setting, showed that baricitinib and pulse steroids combination was associated with a lower mortality rate paralleled by a prompt reduction of inflammatory biomarkers. These results shed new light on the possible usefulness of baricitinib for the treatment of rapidly progressive ILD in patients with systemic autoimmunity and hyper-inflammation.Disclosure of InterestsNone declared
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