Antibody fragments of moderate affinity (approximately microM) can be isolated from repertoires of approximately 10(8) immunoglobulin genes by phage display and rounds of selection with antigen, and the affinities improved by further rounds of mutation and selection. Here, as an alternative strategy, we attempted to isolate high affinity human antibodies directly from large repertoires. We first created highly diverse repertoires of heavy and light chains entirely in vitro from a bank of human V gene segments and then, by recombination of the repertoires in bacteria, generated a large (close to 6.5 × 10(10)) synthetic repertoire of Fab fragments displayed on filamentous phage. From this repertoire we isolated Fab fragments which bound to a range of different antigens and haptens, and with affinities comparable with those of antibodies from a secondary immune response in mice (up to 4 nM). Although the VH‐26 (DP‐47) segment was the most commonly used segment in both artificial and natural repertoires, there were also major differences in the pattern of segment usage. Such comparisons may help dissect the contributions of biological mechanisms and structural features governing V gene usage in vivo.

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To provide the building blocks for making synthetic antibody fragments we have used the polymerase chain reaction (PCR) to clone human variable (V) gene segments of lambda light chains. The PCR primers were based on the sequences of known human V lambda segments, and were used to isolate 14 new V lambda segments (including 4 pseudogenes) from a single individual. We have compiled a sequence directory from this data and other sources to include all known human V lambda segments with open reading frames and we have identified a new V lambda family (V lambda IX). Almost all of the segments (22/24) have different sequences in the complementarity-determining regions, setting a lower limit to the structural diversity of the antigen binding sites encoded by human V lambda genes in the human population.

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Background The spread of SARS-CoV-2 and the COVID-19 pandemic have caused significant morbidity and mortality worldwide. The clinical characteristics and outcomes of hospitalized patients with SARS-CoV-2 and HIV co-infection remain uncertain. Methods We conducted a matched retrospective cohort study of adults hospitalized with a COVID-19 illness in New York City between March 3, 2020 and May 15, 2020. We matched 30 people living with HIV (PLWH) with 90 control group patients without HIV based on age, sex, and race/ethnicity. Using electronic health record data, we compared demographic characteristics, clinical characteristics, and clinical outcomes between PLWH and control patients. Results In our study, the median age was 60.5 years (IQR 56.6–70.0), 20% were female, 27% were White, 30% were Black, and 24% were of Hispanic/Latino ethnicity. There were no significant differences between PLWH and control patients in presenting symptoms, duration of symptoms prior to hospitalization, laboratory markers, or radiographic findings on chest x-ray. More patients without HIV required a higher level of supplemental oxygen on presentation than PLWH. There were no differences in the need for invasive mechanical ventilation during hospitalization, length of stay, or in-hospital mortality. Conclusions The clinical manifestations and outcomes of COVID-19 among patients with SARS-CoV-2 and HIV co-infection were not significantly different than patients without HIV co-infection. However, PLWH were hospitalized with less severe hypoxemia, a finding that warrants further investigation.

Summary Background Hidradenitis suppurativa (HS) is now recognized as a systemic inflammatory disease, sharing molecular similarities with psoriasis. Direct comparison of the systemic inflammation in HS with psoriasis is lacking. Objectives To evaluate the serum proteome of HS and psoriasis, and to identify biomarkers associated with disease severity. Methods In this cross‐sectional study, 1536 serum proteins were assessed using the Olink Explore (Proximity Extension Assay) high‐throughput panel in patients with moderate‐to‐severe HS (n = 11), patients with psoriasis (n = 10) and age‐ and body mass index‐matched healthy controls (n = 10). Results HS displayed an overall greater dysregulation of circulating proteins, with 434 differentially expressed proteins (absolute fold change ≥ 1·2; P ≤ 0·05) in patients with HS vs. controls, 138 in patients with psoriasis vs. controls and 503 between patients with HS and patients with psoriasis. Interleukin (IL)‐17A levels and T helper (Th)1/Th17 pathway enrichment were comparable between diseases, while HS presented greater tumour necrosis factor‐ and IL‐1β‐related signalling. The Th17‐associated markers peptidase inhibitor 3 (PI3) and lipocalin 2 (LCN2) were able to differentiate psoriasis from HS accurately. Both diseases presented increases of atherosclerosis‐related proteins. Robust correlations between clinical severity scores and immune and atherosclerosis‐related proteins were observed across both diseases. Conclusions HS and psoriasis share significant Th1/Th17 enrichment and upregulation of atherosclerosis‐related proteins. Despite the greater body surface area involved in psoriasis, HS presents a greater serum inflammatory burden.

Hidradenitis suppurativa (HS), also known as acne inversa, is a chronic inflammatory skin disease with still largely unknown pathogenesis. While infectious organisms have been identified in lesions of the disease since the 1980s, questions remain over the role that bacteria and microbiome play. Recent studies using 16S ribosomal RNA gene sequencing and larger culture-based studies have begun to paint a clearer picture of the microbial world of HS. With this systematic review, we summarize all the work that has been done to date in HS bacteriology, analyse potential pitfalls and limitations of the current studies, and address future directions of investigation. This systematic review attempted to collate and analyse all bacteriology studies done to date. This review was prospectively registered with PROSPERO ( 1670769) performed in line with the PRISMA checklist. Twenty two studies were identified comprising 862 individual HS patients for culture studies and 206 HS patients for 16S rRNA gene sequencing studies. Methodology tended to be varied, with different sampling, culturing and sequencing methods as well as amount of analysis and stratification of patients. Bacteria identified as elevated in HS lesions in sequencing studies as well as grown from HS lesions in culture studies are identified and discussed. These primarily included the anerobic Gram-negative bacilli Prevotella, Porphyromonas and Fusibacterium, the Gram-positive bacilli Corynebacterium, and the Gram-positive cocci Staphylococcus, Streptococcus and Parvimonas. Potential interactions, as well as work in other disease models with related bacteria are also discussed. Areas of further investigation include in vitro studies of interactions between bacteria and keratinocytes, gut and oral microbiome studies and deep sequencing studies for virulence and phage factors.