In vitro studies on human IgD. II. IgD-secreting cells preferentially elaborate IgD, lambda molecules

The "IgD paradox" describes the unexpected finding that, despite a predominance of kappa (kappa) light (L) chains on the surface of IgD+ human B cells, the majority of monoclonal IgD proteins are of lambda (lambda) type. This potentially informative phenomenon appears to be based on a preferential association between delta (delta) heavy (H) and lambda L chains of IgD-secreting cells. The current studies analyze the phenomenon in vitro. Initial assays on tonsil "spent" supernatants showed that the higher IgD-"externalizing" cultures displayed progressively elevated IgD, lambda/kappa ratios due to parallel shifts in total IgD and IgD, lambda while IgD, kappa remained stable. The cells of the same higher-IgD cultures demonstrated that individual IgD-containing cells had a predominance of lambda chains in contrast to IgM-containing cells of the same cultures using fluorochrome-antibody double staining. Certain tonsil culture IgD-containing cells remarkably appeared to have exclusively lambda chain. These same tonsils show evidence of IgD secretion (Litwin, S. D. and Zehr, B. D., Eur. J. Immunol. 1987. 17:483); thus, these data align preferential delta-lambda chain association with IgD-secreting normal tonsil B cells in vitro and emphasize the usefulness of IgD, lambda/kappa ratio in monitoring IgD secretion. In another approach the relationship between the cellular location of IgD and the preferential delta-lambda chain association was studied using Triton X-114-partitioned cell lysates. IgD, lambda/kappa ratios were one or less in the detergent phase (membrane-enriched fraction) consistent with expected IgD, kappa predominance in membrane IgD. In contrast, the aqueous phase (intracellular-enriched fraction) of IgD-secreting cultures had 2-4 times higher supernatant IgD, lambda/kappa ratios. The restriction of high IgD, lambda/kappa ratios to intracellular fractions and supernatants of IgD-secreting cultured cells parallels the predicted distribution of secretory IgD. In sera studies, the correlation between total IgD and IgD, lambda/kappa ratio values was consistent with secreted sera IgD showing preferential lambda chain expression. It was concluded that the phenomenon of delta-lambda chain preferential association is expressed in vitro as well as in vivo; a property of normal, nonmalignant human IgD-secreting B cells; and closely related to the secretory form of IgD. In certain cultures, the delta-lambda chain preference was so striking as to imply limited heterogeneity of the IgD immune response.     

Undernutrition is associated with mortality,exacerbation, and poorer quality of life in patients with chronic obstructive pulmonary disease: A systematic review with meta-analysis of observational studies

Impaired nutrition status is recognized as a risk factor for worse clinical outcomes in patients with chronic obstructive pulmonary disease (COPD). The aims of this study were to investigate how undernutrition is diagnosed, its prevalence, and whether there is an association between this condition and clinical outcomes in patients with COPD. The search for this systematic review of observational studies (PROSPERO: CRD42020191888) was performed in the PubMed, Embase, and Scopus databases, with no date or language restrictions. The studies had to report data on the diagnosis of undernutrition and its association with mortality, exacerbation, length of hospital stay, or quality of life in adult patients with COPD. A meta-analysis with a random-effects model was performed to combine data. Forty-nine studies were included (20 of them classified as having a low risk of bias), and the most common diagnostic method of undernutrition was body mass index (BMI) (n = 36). The pooled prevalence of undernutrition was equal to 20% (95% CI, 0.15–0.25; I² = 100%), and it was associated with mortality (risk ratio = 1.97; 95% CI, 1.55–2.50; I² = 98%), exacerbation (risk ratio = 1.73; 95% CI, 1.03–2.91; I² = 96%), and poorer quality of life (mean difference = 8.25; 95% CI, 5.40–11.10; I² = 79%). For all outcomes, the certainty of evidence was very low. In conclusion, undernutrition is prevalent and is associated with poorer outcomes in patients with COPD. However, undernutrition is mainly diagnosed by BMI, which underreports its prevalence, and the certainty of the evidence is very low.