Variable stars in the ultra-faint dwarf spheroidal galaxy Ursa Major I

We have performed the first study of the variable star population of Ursa Major I (UMa I), an ultra-faint dwarf satellite recently discovered around the Milky Way by the Sloan Digital Sky Survey. Combining time series observations in the B and V bands from four different telescopes, we have identified seven RR Lyrae stars in UMa I, of which five are fundamental-mode (RRab) and two are first-overtone pulsators (RRc). Our V, B-V color-magnitude diagram of UMa I reaches V~23 mag (at a signal-to-noise ratio of ~ 6) and shows features typical of a single old stellar population. The mean pulsation period of the RRab stars = 0.628, {\sigma} = 0.071 days (or = 0.599, {\sigma} = 0.032 days, if V4, the longest period and brightest variable, is discarded) and the position on the period-amplitude diagram suggest an Oosterhoff-intermediate classification for the galaxy. The RR Lyrae stars trace the galaxy horizontal branch at an average apparent magnitude of = 20.43 +/- 0.02 mag (average on 6 stars and discarding V4), giving in turn a distance modulus for UMa I of (m-M)0 = 19.94 +/- 0.13 mag, distance d= 97.3 +6.0/-5.7 kpc, in the scale where the distance modulus of the Large Magellanic Cloud is 18.5 +/- 0.1 mag. Isodensity contours of UMa I red giants and horizontal branch stars (including the RR Lyrae stars identified in this study) show that the galaxy has an S-shaped structure, which is likely caused by the tidal interaction with the Milky Way. Photometric metallicities were derived for six of the UMa I RR Lyrae stars from the parameters of the Fourier decomposition of the V-band light curves, leading to an average metal abundance of [Fe/H] = -2.29 dex ({\sigma} = 0.06 dex, average on 6 stars) on the Carretta et al. metallicity scale.Comment: Accepted for publication in Ap

Atopic dermatitis and ulcerative colitis successfully treated with upadacitinib

Background and Objectives: JAK inhibitors entered current clinical practice as treatment for several immune-related diseases and, recently, for atopic dermatitis. These drugs target the Janus Kinase intracellular cascade, rendering them suitable for treating both Th1 and Th2 immune-mediated responses. Materials and Methods: We report the case of a 36-year-old male patient presenting an overlap of ulcerative colitis, a Th1-related disease, and atopic dermatitis, a Th2-mediated condition. Treatment with upadacitinib was initiated, and laboratory and instrumental follow-ups were carried out for 8 months. Results: The complete and persistent clinical remission of both conditions was observed at a low dose of 15 mg of upadacitinib, even though ulcerative colitis guidelines usually recommend a dosage of 45 mg. No serious adverse responses to therapy were reported. Conclusions: Upadacitinib may be the most suitable management strategy in subjects with coexisting severe conditions mediated by Th1 inflammation, such as ulcerative colitis, and by Th2 cytokines, such as atopic dermatitis

Serum immunoglobulin G (IgG) subclasses in a cohort of systemic sclerosis patients

Objectives: To assess serum immunoglobulin G (IgG) subclasses in a cohort of systemic sclerosis (SSc) patients and to evaluate the influence of IgG subclasses in the main complications of the disease. Methods: The serum level of IgG subclasses was evaluated in 67 SSc patients and 48 healthy controls (HC), matched for sex and age. Serum samples were collected and measured IgG1–4 subclasses by turbidimetry. Results: SSc patients had lower median total IgG [9.88 g/l (IQR 8.18–11.42 g/l) vs. 12.09 g/l (IQR 10.24–13.54 g/l), p < 0.001], IgG1 [5.09 g/l (IQR 4.25–6.38 g/l) vs. 6.03 g/l (IQR 5.39–7.90 g/l), p < 0.001], and IgG3 [0.59 g/l (IQR 0.40–0.77 g/l) vs. 0.80 g/l (IQR 0.46–1 g/l), p < 0.05] serum levels compared to HC. The logistic regression analysis showed IgG3 as the only variable associated with the diffusing capacity of the lung for carbon monoxide (DLco) ≤60% of the predicted [OR 9.734 (CI 95%: 1.312–72.221), p < 0.05] and modified Rodnan skin score (mRSS) [OR 1.124 (CI 95%: 1.019–1.240), p < 0.05], anti-topoisomerase I [OR 0.060 (CI 95%: 0.007–0.535), p < 0.05], and IgG3 [OR 14.062 (CI 95%: 1.352–146.229), p < 0.05] as variables associated with radiological interstitial lung disease (ILD). Conclusion: SSc patients have reduced levels of total IgG and an altered IgG subclass distribution compared to HC. Moreover, SSc patients show different serum IgG subclasses profiles according to the main involvement of the disease

SARS-CoV-2 Vaccine Induced Atypical Immune Responses in Antibody Defects: Everybody Does their Best

Background: Data on immune responses to SARS-CoV-2 in patients with Primary Antibody Deficiencies (PAD) are limited to infected patients and to heterogeneous cohorts after immunization. Methods: Forty-one patients with Common Variable Immune Deficiencies (CVID), six patients with X-linked Agammaglobulinemia (XLA), and 28 healthy age-matched controls (HD) were analyzed for anti-Spike and anti-receptor binding domain (RBD) antibody production, generation of Spike-specific memory B-cells, and Spike-specific T-cells before vaccination and one week after the second dose of BNT162b2 vaccine. Results: The vaccine induced Spike-specific IgG and IgA antibody responses in all HD and in 20% of SARS-CoV-2 naive CVID patients. Anti-Spike IgG were detectable before vaccination in 4 out 7 CVID previously infected with SARS-CoV-2 and were boosted in six out of seven patients by the subsequent immunization raising higher levels than patients naïve to infection. While HD generated Spike-specific memory B-cells, and RBD-specific B-cells, CVID generated Spike-specific atypical B-cells, while RBD-specific B-cells were undetectable in all patients, indicating the incapability to generate this new specificity. Specific T-cell responses were evident in all HD and defective in 30% of CVID. All but one patient with XLA responded by specific T-cell only. Conclusion: In PAD patients, early atypical immune responses after BNT162b2 immunization occurred, possibly by extra-follicular or incomplete germinal center reactions. If these responses to vaccination might result in a partial protection from infection or reinfection is now unknown. Our data suggests that SARS-CoV-2 infection more effectively primes the immune response than the immunization alone, possibly suggesting the need for a third vaccine dose for patients not previously infected

Might IgA be a biomarker of disease activity in Takayasu arteritis

Takayasu arteritis is a systemic vasculitis of the large vessels and mainly affects Japanese and Southeast Asian women in the second and third decades of life. Inflammatory infiltrate affects the full thickness of the vessel wall, inducing progressive lumen stenosis and occlusion. The main biomarkers of disease activity are the ESR, CRP and serum levels of circulating cytokines. This case report describes the clinical history of a young woman with Takayasu disease with high serum levels of IgA at onset. IgA remained elevated with persistence of disease activity, and normalized only when the patient was treated with an anti-TNF agent (infliximab), which also induced a clinical response in the vasculitis. IgA levels, together with other inflammatory parameters, may be considered a biomarker of disease activity. Learning points: This case report highlights the need to increase the number of humoral markers used to assess disease course in Takayasu arteritis (TA).IgA may be considered a biomarker of TA disease activity.Serum IgA levels may be helpful to identify TA patients not responding to traditional therapy

Serum Immunoglobulin G (IgG) Subclasses in a Cohort of Systemic Sclerosis Patients

Objectives: To assess serum immunoglobulin G (IgG) subclasses in a cohort of systemic sclerosis (SSc) patients and to evaluate the influence of IgG subclasses in the main complications of the disease. Methods: The serum level of IgG subclasses was evaluated in 67 SSc patients and 48 healthy controls (HC), matched for sex and age. Serum samples were collected and measured IgG1-4 subclasses by turbidimetry. Results: SSc patients had lower median total IgG [9.88 g/l (IQR 8.18-11.42 g/l) vs. 12.09 g/l (IQR 10.24-13.54 g/l), p < 0.001], IgG1 [5.09 g/l (IQR 4.25-6.38 g/l) vs. 6.03 g/l (IQR 5.39-7.90 g/l), p < 0.001], and IgG3 [0.59 g/l (IQR 0.40-0.77 g/l) vs. 0.80 g/l (IQR 0.46-1 g/l), p < 0.05] serum levels compared to HC. The logistic regression analysis showed IgG3 as the only variable associated with the diffusing capacity of the lung for carbon monoxide (DLco) ≤60% of the predicted [OR 9.734 (CI 95%: 1.312-72.221), p < 0.05] and modified Rodnan skin score (mRSS) [OR 1.124 (CI 95%: 1.019-1.240), p < 0.05], anti-topoisomerase I [OR 0.060 (CI 95%: 0.007-0.535), p < 0.05], and IgG3 [OR 14.062 (CI 95%: 1.352-146.229), p < 0.05] as variables associated with radiological interstitial lung disease (ILD). Conclusion: SSc patients have reduced levels of total IgG and an altered IgG subclass distribution compared to HC. Moreover, SSc patients show different serum IgG subclasses profiles according to the main involvement of the disease

COVID-19 and Mixed Cryoglobulinemia Syndrome: Long-Term Survey Study on the Prevalence and Outcome, Vaccine Safety, and Immunogenicity

PurposeMixed cryoglobulinemia syndrome (MCs) is a rare immunoproliferative systemic disorder with cutaneous and multiple organ involvement. Our multicenter survey study aimed to investigate the prevalence and outcome of COVID-19 and the safety and immunogenicity of COVID-19 vaccines in a large MCs series.MethodsThe survey included 430 unselected MCs patients (130 M, 300 F; mean age 70 +/- 10.96 years) consecutively collected at 11 Italian referral centers. Disease classification, clinico-serological assessment, COVID-19 tests, and vaccination immunogenicity were carried out according to current methodologies.ResultsA significantly higher prevalence of COVID-19 was found in MCs patients compared to Italian general population (11.9% vs 8.0%, p < 0.005), and the use of immunomodulators was associated to a higher risk to get infected (p = 0.0166). Moreover, higher mortality rate was recorded in MCs with COVID-19 compared to those without (p < 0.01). Patients' older age (>= 60 years) correlated with worse COVID-19 outcomes. The 87% of patients underwent vaccination and 50% a booster dose. Of note, vaccine-related disease flares/worsening were significantly less frequent than those associated to COVID-19 (p = 0.0012). Impaired vaccination immunogenicity was observed in MCs patients compared to controls either after the first vaccination (p = 0.0039) and also after the booster dose (p = 0.05). Finally, some immunomodulators, namely, rituximab and glucocorticoids, hampered the vaccine-induced immunogenicity (p = 0.029).ConclusionsThe present survey revealed an increased prevalence and morbidity of COVID-19 in MCs patients, as well an impaired immunogenicity even after booster vaccination with high rate of no response. Therefore, MCs can be included among frail populations at high risk of infection and severe COVID-19 manifestations, suggesting the need of a close monitoring and specific preventive/therapeutical measures during the ongoing pandemic