Objective The replacement of standard immunofluorescence anti-nuclear antibody (ANA) methods with bead-based assays is a new clinical option. A large, multi-racial cohort of SLE patients, blood relatives and unaffected control individuals was evaluated for familial aggregation and subset clustering of autoantibodies by high-throughput serum screening technology and traditional methods. Methods Serum samples (1,540 SLE patients, 1,127 unaffected relatives, and 906 healthy, population-based controls) were analyzed for SLE autoantibodies using a bead-based assay, immunofluorescence, and immunodiffusion. Autoantibody prevalence, disease sensitivity, clustering, and association with standard immunodiffusion results were evaluated. Results ANA frequency in SLE patient sera were 89%, 73%, and 67% by BioPlex 2200 and 94%, 84%, and 86% by immunofluorescence in African-American, Hispanic, and European-American patients respectively. 60kD Ro, La, Sm, nRNP A, and ribosomal P prevalence were compared across assays, with sensitivities ranging from 0.92 to 0.83 and specificities ranging from 0.90 to 0.79. Cluster autoantibody analysis showed association of three subsets: 1) 60kD Ro, 52kD Ro and La, 2) spliceosomal proteins, and 3) dsDNA, chromatin, and ribosomal P. Familial aggregation of Sm/RNP, ribosomal P, and 60kD Ro in SLE patient sibling pairs was observed (p ≤ 0.004). Simplex pedigree patients had a greater prevalence for dsDNA (p=0.0003) and chromatin (p=0.005) autoantibodies than multiplex patients. Conclusion ANA frequencies detected by a bead-based assay are lower in European-American SLE patients compared to immunofluorescence. These assays have strong positive predictive values across racial groups, provide useful information for clinical care, and provide unique insights to familial aggregation and autoantibody clustering.

We targeted LYN, a src-tyosine kinase involved in B-cell activation, in case-control association studies using populations of European-American, African-American and Korean subjects. Our combined European-derived population, consisting of 2463 independent cases and 3131 unrelated controls, shows significant association with rs6983130 in a female-only analysis with 2254 cases and 2228 controls (P ¼ 1.1 Â 10 À4 , odds ratio (OR) ¼ 0.81 (95% confidence interval: 0.73-0.90)). This single nucleotide polymorphism (SNP) is located in the 5 0 untranslated region within the first intron near the transcription initiation site of LYN. In addition, SNPs upstream of the first exon also show weak and sporadic association in subsets of the total EuropeanAmerican population. Multivariate logistic regression analysis implicates rs6983130 as a protective factor for systemic lupus erythematosus (SLE) susceptibility when anti-dsDNA, anti-chromatin, anti-52 kDa Ro or anti-Sm autoantibody status were used as covariates. Subset analysis of the European-American female cases by American College of Rheumatology classification criteria shows a reduction in the risk of hematological disorder with rs6983130 compared with cases without hematological disorders (P ¼ 1.5 Â 10 À3 , OR ¼ 0.75 (95% CI: 0.62À0.89)). None of the 90 SNPs tested show significant association with SLE in the African American or Korean populations. These results support an association of LYN with European-derived individuals with SLE, especially within autoantibody or clinical subsets.

Systemic lupus erythematosus (SLE) is an autoimmune disease with highly variable clinical presentation. Patients suffer from immunological abnormalities that target T-cell, B-cell and accessory cell functions. B cells are hyperactive in SLE patients. An adapter protein expressed in B cells called BANK1 (B-cell scaffold protein with ankyrin repeats) was reported in a previous study to be associated with SLE in a European population. The objective of this study was to assess the BANK1 genotypephenotype association in an independent replication sample. We genotyped 38 single nucleotide polymorphisms (SNPs) in BANK1 on 1892 European-derived SLE patients and 2652 European-derived controls. The strongest associations with SLE and BANK1 were at rs17266594 (corrected P-value ¼ 1.97 Â 10 À5 , odds ratio (OR) ¼ 1.22, 95% CI 1.12-1.34) and rs10516487 (corrected P-value ¼ 2.59 Â 10 À5 , OR ¼ 1.22, 95% CI 1.11-1.34). Our findings suggest that the association is explained by these two SNPs, confirming previous reports that these polymorphisms contribute to the risk of developing lupus. Analysis of patient subsets enriched for hematological, immunological and renal ACR criteria or the levels of autoantibodies, such as anti-RNP A and anti-SmRNP, uncovers additional BANK1 associations. Our results suggest that BANK1 polymorphisms alter immune system development and function to increase the risk for developing lupus.

Background: Inflammatory bowel disease (IBD) [i.e., Crohn’s disease (CD) and ulcerative colitis (UC)] has been considered a relative contraindication for radiation therapy (RT) to the abdomen or pelvis, potentially preventing patients with a diagnosis of IBD from receiving definitive therapy for their malignancy. Method: Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) conventions, a PubMed/MEDLINE literature search was conducted using the keywords RT, brachytherapy, inflammatory bowel disease, Crohn’s disease, ulcerative colitis and toxicity. Results: A total of 1,206 publications were screened with an addition of 8 studies identified through hand searching. Nineteen studies met the inclusion criteria for quantitative analysis. The total population across all studies was 497 patients, 50·5% having UC, 37% having CD and an additional 12·5% having unspecified IBD. Primary gastrointestinal malignancy (55%) followed by prostate cancer (40%) composed the bulk of the population. Acute and late grade 3 or greater gastrointestinal specific toxicity ranged from 0–23% to 0–13% respectively for those patients with IBD treated with RT to the abdomen or pelvis. In the literature reviewed, RT does not appear to increase fistula or stricture formation or IBD flares; however, one study did note RT to be a statistically significant risk factor for subsequent IBD flare on multivariate analysis. Conclusions: A review of reported acute and late toxicities suggests that patients with IBD should still be considered for definitive radiotherapy. Patient characteristics including IBD distribution relative to the irradiated field, inflammatory activity at the time of radiation, overall disease severity and disease phenotype in the case of CD (fistulising versus stricturing versus inflammatory only) should be considered on an individual basis when evaluating potential patients. When possible, advanced techniques with strict organ at risk dose constraints should be employed to limit toxicity in this patient population.

Introduction: This study aims to look at the trends in our head and neck cancer patient population over the past 5 years with an emphasis on the past 2 years to evaluate how the coronavirus disease 2019 (COVID-19) pandemic has impacted our disparities and availability of care for patients, especially those living in rural areas. An additional aim is to identify existing disparities at our institution in the treatment of head and neck patients and determine solutions to improve patient care. Materials and Methods: A retrospective chart review was performed to identify patients who were consulted and subsequently treated with at least one fraction of radiation therapy at our institution with palliative or curative intent. Patient demographic information was collected including hometown, distance from the cancer centre based on zip-codes and insurance information and type of appointment (in-person or telehealth). Rural–urban continuum codes were used to determine rurality. Results: A total of 490 head and neck cancer patients (n = 490) were treated from 2017 to 2021. When broken down by year, there were no significant trends in patient population regarding travel distance or rurality. Roughly 20–30% of our patients live in rural areas and about 30% have a commute > 50 miles for radiation treatment. A majority of our patients rely on public insurance (68%) with a small percentage of those uninsured (4%). Telehealth visits were rare prior to 2019 and rose to 5 and 2 visits in 2020 and 2021, respectively. Conclusions: Head and neck cancer patients, despite rurality or distance from a cancer centre, may present with alarmingly enough symptoms despite limitations and difficulties with seeking medical attention even during the COVID-19 pandemic in 2020. However, providers must be aware of these potential disparities that exist in the rural population and seek to address these.