T Cell Calcium Flux And Clonal Proliferation Report On Antigen-Specific Myeloid Cell Encounters

Despite its clinical success, the mechanism underlying extracorporeal photopheresis (ECP) is not well understood, however, the plate-passage (PP) step appears integral to generating activated monocytes. In the first part of the project, we developed a functional assay to evaluate the efficacy of plate-passed myeloid cells (PPM) compared with freshly isolated, unstimulated monocytes (UM) and conventional dendritic cells derived from blood monocytes cultured with GM-CSF/IL4 (DC). Each of these three antigen presenting cell (APC) was co-cultured with purified, autologous CD8 cells, with or without CD4 cells. Cultures were carried out using melanoma antigen MART-1 long peptide (LP), a 25-amino acid peptide containing the binding sequences for the appropriate MHC class I and II, and for presentation to CD8+ and CD4+ cells. Results showed reliable expansions of freshly isolated naïve human T cells using the three types of APC, without any significant differences among the types, and the addition of CD4+ tended to enhance expansion of PPM and DC, but not UM. In the second part, we sought to develop a method for directly tracking early T cell responses during immunotherapy. Using calcium flux to indicate early T cell signaling, we focused mostly on the ovalbumin (OVA)-derived, SIINFEKL-specific transgenic mouse model (OT1). After a few protocol modifications, we were able to detect antigen-specific calcium flux (ASF) upon mixing naïve OT1 cells with SIINFEKL peptide-loaded DC compared with non-specific peptide counterparts. We could still detect ASF down to a peptide-loading concentration of ~10-3uM and at a frequency of ~0.1% OT1 cells among wild-type (WT), non-responding cells. We next identified the activation requirements of early effector and memory OT1 cells from the spleen, lymph nodes, and peripheral blood after adoptive transfer into WT recipients immunized with OVA. At 1 week, OT1 cells from all 3 tissues had become activated, effector cells (CD44hi and CD62 lo), and while detectable, ASF in all three tissues was reduced compared with naïve cells. At 6 weeks, only the peripheral blood OT1 cells had generated a memory response (CD127hi KLRG1lo), and ASF in all three tissues was further reduced. Herein, we have shown that ASF can be detected in naïve, and less so antigen-experienced and memory T cells in a single-antigen, transgenic system from which we hope to develop a multi-antigen tumor model

HLA Allele Associations and V-Beta T-Lymphocyte Expansions in Patients With Psoriasis, Harboring Toxin-Producing Staphylococcus aureus

HLA alleles have been associated with psoriasis. Toxin-producing strains of Staphylococcus aureus behave as superantigens, and if present in patients, might play a role in the exacerbation of psoriatic lesions by activating certain V-beta (Vβ) T-lymphocyte subsets. Allele frequencies in 22 patients and 22 controls (alleles determined by DNA/SSP typing) were used to calculate a relative risk of 4.7 (P < .05) for HLA-Cw6. S aureus was isolated from the throat of 11 patients. Enterotoxins A and C were detected by agglutination in the culture filtrate of one isolate. The enterotoxin A and/or C genes were detected by PCR in 9 isolates, and transcripts were detected by RT-PCR in 7 of them. None of the isolates from controls harbored enterotoxin genes. Vβ expansions were detected by RT-PCR in all 22 patients. Low or no Vβ expansions were obtained in controls. The association of HLA-Cw6 with psoriasis in Lebanese concurs with that reported for other ethnic groups. Toxin-producing isolates that colonize patients might play a role in the exacerbation of psoriatic lesions

Eruptive melanocytic nevi heralding the diagnosis of metastatic malignant melanoma: A case report

Digitalitzat per Artypla

Impaired health-related quality of life in idiopathic inflammatory myopathies : a cross-sectional analysis from the COVAD-2 e-survey

OBJECTIVES To investigate health-related quality of life in patients with idiopathic inflammatory myopathies (IIMs) compared with those with non-IIM autoimmune rheumatic diseases (AIRDs), non-rheumatic autoimmune diseases (nrAIDs) and without autoimmune diseases (controls) using Patient-Reported Outcome Measurement Information System (PROMIS) instrument data obtained from the second COVID-19 vaccination in autoimmune disease (COVAD-2) e-survey database. METHODS Demographics, diagnosis, comorbidities, disease activity, treatments and PROMIS instrument data were analysed. Primary outcomes were PROMIS Global Physical Health (GPH) and Global Mental Health (GMH) scores. Factors affecting GPH and GMH scores in IIMs were identified using multivariable regression analysis. RESULTS We analysed responses from 1582 IIM, 4700 non-IIM AIRD and 545 nrAID patients and 3675 controls gathered through 23 May 2022. The median GPH scores were the lowest in IIM and non-IIM AIRD patients {13 [interquartile range (IQR) 10-15] IIMs vs 13 [11-15] non-IIM AIRDs vs 15 [13-17] nrAIDs vs 17 [15-18] controls, P < 0.001}. The median GMH scores in IIM patients were also significantly lower compared with those without autoimmune diseases [13 (IQR 10-15) IIMs vs 15 (13-17) controls, P < 0.001]. Inclusion body myositis, comorbidities, active disease and glucocorticoid use were the determinants of lower GPH scores, whereas overlap myositis, interstitial lung disease, depression, active disease, lower PROMIS Physical Function 10a and higher PROMIS Fatigue 4a scores were associated with lower GMH scores in IIM patients. CONCLUSION Both physical and mental health are significantly impaired in IIM patients, particularly in those with comorbidities and increased fatigue, emphasizing the importance of patient-reported experiences and optimized multidisciplinary care to enhance well-being in people with IIMs

Early experience of COVID-19 vaccination in adults with systemic rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance Vaccine Survey.

Background: We describe the early experiences of adults with systemic rheumatic disease who received the COVID-19 vaccine. Methods: From 2 April to 30 April 2021, we conducted an online, international survey of adults with systemic rheumatic disease who received COVID-19 vaccination. We collected patient-reported data on clinician communication, beliefs and intent about discontinuing disease-modifying antirheumatic drugs (DMARDs) around the time of vaccination, and patient-reported adverse events after vaccination. Results: We analysed 2860 adults with systemic rheumatic diseases who received COVID-19 vaccination (mean age 55.3 years, 86.7% female, 86.3% white). Types of COVID-19 vaccines were Pfizer-BioNTech (53.2%), Oxford/AstraZeneca (22.6%), Moderna (21.3%), Janssen/Johnson & Johnson (1.7%) and others (1.2%). The most common rheumatic disease was rheumatoid arthritis (42.3%), and 81.2% of respondents were on a DMARD. The majority (81.9%) reported communicating with clinicians about vaccination. Most (66.9%) were willing to temporarily discontinue DMARDs to improve vaccine efficacy, although many (44.3%) were concerned about rheumatic disease flares. After vaccination, the most reported patient-reported adverse events were fatigue/somnolence (33.4%), headache (27.7%), muscle/joint pains (22.8%) and fever/chills (19.9%). Rheumatic disease flares that required medication changes occurred in 4.6%. Conclusion: Among adults with systemic rheumatic disease who received COVID-19 vaccination, patient-reported adverse events were typical of those reported in the general population. Most patients were willing to temporarily discontinue DMARDs to improve vaccine efficacy. The relatively low frequency of rheumatic disease flare requiring medications was reassuring

Prolonged COVID-19 symptom duration in people with systemic autoimmune rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance Vaccine Survey

OBJECTIVE: We investigated prolonged COVID-19 symptom duration, defined as lasting 28 days or longer, among people with systemic autoimmune rheumatic diseases (SARDs). METHODS: We analysed data from the COVID-19 Global Rheumatology Alliance Vaccine Survey (2 April 2021-15 October 2021) to identify people with SARDs reporting test-confirmed COVID-19. Participants reported COVID-19 severity and symptom duration, sociodemographics and clinical characteristics. We reported the proportion experiencing prolonged symptom duration and investigated associations with baseline characteristics using logistic regression. RESULTS: We identified 441 respondents with SARDs and COVID-19 (mean age 48.2 years, 83.7% female, 39.5% rheumatoid arthritis). The median COVID-19 symptom duration was 15 days (IQR 7, 25). Overall, 107 (24.2%) respondents had prolonged symptom duration (≥28 days); 42/429 (9.8%) reported symptoms lasting ≥90 days. Factors associated with higher odds of prolonged symptom duration included: hospitalisation for COVID-19 vs not hospitalised and mild acute symptoms (age-adjusted OR (aOR) 6.49, 95% CI 3.03 to 14.1), comorbidity count (aOR 1.11 per comorbidity, 95% CI 1.02 to 1.21) and osteoarthritis (aOR 2.11, 95% CI 1.01 to 4.27). COVID-19 onset in 2021 vs June 2020 or earlier was associated with lower odds of prolonged symptom duration (aOR 0.42, 95% CI 0.21 to 0.81). CONCLUSION: Most people with SARDs had complete symptom resolution by day 15 after COVID-19 onset. However, about 1 in 4 experienced COVID-19 symptom duration 28 days or longer; 1 in 10 experienced symptoms 90 days or longer. Future studies are needed to investigate the possible relationships between immunomodulating medications, SARD type/flare, vaccine doses and novel viral variants with prolonged COVID-19 symptoms and other postacute sequelae of COVID-19 among people with SARDs