Human leukocyte antigen (HLA) typing from next generation sequencing (NGS) data has the potential for widespread applications. Here we introduce a novel tool (HLAreporter) for HLA typing from NGS data based on read-mapping using a comprehensive reference panel containing all known HLA alleles, followed by de novo assembly of the gene-specific short reads. Accurate HLA typing at high-digit resolution was achieved when it was tested on publicly available NGS data, outperforming other newly developed tools such as HLAminer and PHLAT. HLAreporter can be downloaded from http://paed.hku.hk/genome/.

An early sepsis-induced acute kidney injury (sepsis-AKI) biomarker is currently in needed. Urinary neutrophil gelatinase-associated lipocalin (uNGAL) is a candidate of sepsis-AKI biomarker but with different cut-point values. Urinary exosomal activating transcriptional factor 3 (uATF3) has been mentioned as an interesting biomarker. We conducted experiments in mice and a prospective, multicenter study in patients as a proof of concept that urine exosome is an interesting biomarker. An early expression of ATF3 in kidney of CD-1 mice at 6 h after cecal ligation and puncture implied the possibility of uATF3 as an early sepsis-AKI biomarker. Increase serum creatinine (Scr) ≥0.3 mg/dL from the baseline was used as an AKI diagnosis and urine was analyzed for uATF3 and uNGAL. Patients with baseline Scr at admission ≥1.5 mg/dL were excluded. The analysis showed higher Scr, uNGAL and uATF3 in patients with sepsis-AKI in comparison with patients with sepsis-non-AKI and healthy volunteers. A fair correlation, r2 = 0.47, between uATF3 and uNGAL was showed in sepsis-AKI group with Scr ≥2 mg/dL. To see if uATF3 could be an early sepsis-AKI biomarker, urine sample was collected daily during the first week of the admission. In sepsis-AKI and sepsis-non-AKI groups, uNGAL were 367 ± 43 ng/mL and 183 ± 23 ng/mL, respectively; and uATF3 were 19 ± 4 ng/mL and 1.4 ± 0.8 ng/mL, respectively. With the mean value of uNGAL and uATF3 in sepsis AKI as a cut-off level, AUROC of uNGAL and uATF3 were 64% (95% CI 0.54 to 0.74) and 84% (95% CI 0.77 to 0.91), respectively. Urine exosome is an interesting source of urine biomarker and uATF3 is an interesting sepsis-AKI biomarker.

Host genetics is a key determinant of COVID-19 outcomes. Previously, the COVID-19 Host Genetics Initiative genome-wide association study used common variants to identify multiple loci associated with COVID-19 outcomes. However, variants with the largest impact on COVID-19 outcomes are expected to be rare in the population. Hence, studying rare variants may provide additional insights into disease susceptibility and pathogenesis, thereby informing therapeutics development. Here, we combined whole-exome and whole-genome sequencing from 21 cohorts across 12 countries and performed rare variant exome-wide burden analyses for COVID-19 outcomes. In an analysis of 5,085 severe disease cases and 571,737 controls, we observed that carrying a rare deleterious variant in the SARS-CoV-2 sensor toll-like receptor TLR7 (on chromosome X) was associated with a 5.3-fold increase in severe disease (95% CI: 2.75–10.05, p = 5.41x10^-7). This association was consistent across sexes. These results further support TLR7 as a genetic determinant of severe disease and suggest that larger studies on rare variants influencing COVID-19 outcomes could provide additional insights.

Introduction: BLyS and APRIL are cytokines from the tumor necrosis factor family which play an important role in systemic lupus erythematosus (SLE). Previous works suggested an association between both molecules and SLE disease activity although their correlation with lupus nephritis is not known. We therefore assessed serum BLyS and APRIL in active lupus nephritis patients. Methods: Serum samples from active lupus nephritis and at 6 months post-treatment were obtained. Serum levels of BLyS and APRIL (n = 47) as well as renal mRNA expression were measured. Serum levels of both molecules and clinical data (n = 27) were available at 6 months follow-up. All biopsy-proven lupus nephritis patients were treated with similar immunosuppressive drugs. Results: Serum levels of APRIL were associated with proteinuria (Rs = 0.44, P value < 0.01) and degree of histological activity (Rs = 0.34; P value < 0.05) whereas BLyS levels were associated with complement levels (Rs = 0.46; P value < 0.01) and dosage of immunosuppressant. Interestingly, serum APRIL as well as its intrarenal mRNA levels were associated with resistance to treatment. From the receiver operating characteristic (ROC) analysis, high levels (> 4 ng/mL) of serum APRIL predicted treatment failure with a positive predictive value of 93 percent. Conclusion: APRIL could be a potential biomarker for predicting difficult-to-treat cases of lupus nephritis.

A greater understanding of the antibody response to SARS-CoV-2 in an infected population is important for the development of a vaccination. To investigate SARS-CoV-2 IgA and IgG antibodies in Thai patients with differing severities of COVID-19. Plasma from the following patient groups was examined: 118 adult patients with confirmed SARS-CoV-2 infections, 49 patients under investigation (without confirmed infections), 20 patients with other respiratory infections, and 102 healthy control patients. Anti-SARS-CoV-2 enzyme-linked immunosorbent assay (ELISA) from EUROIMMUN was performed to assess for IgA and IgG antibodies. The optical density (OD) ratio cutoff for a positive result was 1.1 for IgA and 0.8 for IgG. Additionally, the association of the antibody response with both the severity of disease and the date after onset of symptoms was analyzed. A total of 289 participants were enrolled and 384 samples analyzed from March 10 to May 31, 2020. Patients were categorized, based on their clinical manifestations, as mild (n = 59), moderate (n = 27), or severe (n = 32). The overall sensitivity of IgA and IgG from the samples collected after day 7 of the symptoms was 87.9% (95% CI: 79.8–93.6) and 84.8% (95% CI: 76.2–91.3), respectively. Compared to the mild group, the severe group had significantly higher levels of spike 1 (S1) antigen-specific IgA and IgG. All patients in the moderate and severe groups had S1-specific IgG, while 20% of the patients in the mild group did not have any IgG detected after two weeks after the onset of symptoms. Interestingly, in the severe group, the SARS-CoV-2 IgG level was significantly higher in males than females (p = 0.003). The serological test for SARS-CoV-2 has a high sensitivity more than two weeks after the onset of illness. Additionally, the serological response differs among patients based on sex as well as the severity of infection.

Probiotics may have the potential to protect against breast cancer, partly through systemic immunomodulatory action and active impact upon intestinal microbiota. Given a few clinical studies on their curative role, we conducted a systematic review of the potential effects of probiotics in breast cancer patients and survivors of breast cancer, aiming to support further clinical studies. A literature search was performed using PubMed, Embase, and the CENTRAL databases from inception through to March 2022. A total of eight randomized clinical trials were identified from thirteen articles published between 2004 and 2022. We evaluated quality-of-life measures, observed bacterial species and diversity indices, probiotic-related metabolites, inflammatory biomarkers, and other responses in breast cancer patients and survivors. Results were synthesized qualitatively and quantitatively using random-effects meta-analysis. Different probiotics supplements utilized included Lactobacillus species alone (Lacto), with or without estriol; probiotic combinations of Lactobacillus with Bifidobacterium (ProLB), with or without prebiotic fructooligosaccharides (FOS); ProLB plus Streptococcus and FOS (ProLBS + FOS); and ProLB plus Enterococcus (ProLBE). We found that use of ProLBS with FOS in breast cancer patients and use of ProLBE in survivors of breast cancer show potential benefits in countering obesity and dyslipidemia. ProLBS with FOS use decreases pro-inflammatory TNF-α in breast cancer survivors and improves quality of life in those with breast-cancer-associated lymphedema. Supplementing probiotics capsules (10⁹ CFU) with a prebiotic and using an intake duration of 10 weeks could provide a better approach than probiotics alone.