Prolonged Fever, Hepatosplenomegaly, and Pancytopenia in a 46-Year-Old Woman

Liran Levy and colleagues discuss the differential diagnosis, investigation, and management of a 46-year-old woman with fever, weakness, night sweats, and weight loss

IgTreeZ, A toolkit for immunoglobulin gene lineage tree-based analysis, reveals CDR3s are crucial for selection analysis

Somatic hypermutation (SHM) is an important diversification mechanism that plays a part in the creation of immune memory. Immunoglobulin (Ig) variable region gene lineage trees were used over the last four decades to model SHM and the selection mechanisms operating on B cell clones. We hereby present IgTreeZ (Immunoglobulin Tree analyZer), a python-based tool that analyses many aspects of Ig gene lineage trees and their repertoires. Using simulations, we show that IgTreeZ can be reliably used for mutation and selection analyses. We used IgTreeZ on empirical data, found evidence for different mutation patterns in different B cell subpopulations, and gained insights into antigen-driven selection in corona virus disease 19 (COVID-19) patients. Most importantly, we show that including the CDR3 regions in selection analyses - which is only possible if these analyses are lineage tree-based - is crucial for obtaining correct results. Overall, we present a comprehensive lineage tree analysis tool that can reveal new biological insights into B cell repertoire dynamics.HN was supported by a Bar-Ilan University President’s Scholarship. AC is supported by the Spanish Ministry of Economy and Competitiveness (MINECO) grant RTI2018-093894-B-100. GM is supported by Spanish Institute of Health Carlos III (Miguel Servet grant 2020-2024)

Bone marrow aspirate showing multiple parasites (black arrows) within and released from the monocyte, consistent with the presence of <i>Leishmania</i> amastigotes.

<p>(Giemsa stain.)</p

The patient's diagnosis and treatment over the course of time (<i>x</i>-axis in days).

<p><i>y</i>-axis denotes lactate dehydrogenase (LDH) levels in blue, white blood cell counts (WBC) in red. Black arrows designate hospitalization onset. Green arrows designate bone marrow biopsy (BM) or aspiration, red for liver biopsy (LB).</p

Bone marrow aspirate showing monocytes (red arrows) engulfing red blood cell precursors (black arrows).

<p>(Giemsa stain.)</p

Ethnic variation in medical and lifestyle risk factors for B cell non-Hodgkin lymphoma: A case-control study among Israelis and Palestinians

<div><p>Background</p><p>Risk factors for B-cell non-Hodgkin lymphoma (B-NHL) have not been assessed among Palestinian Arabs (PA) and Israeli Jews (IJ).</p><p>Methods</p><p>In a case-control study we investigated self-reported medical and lifestyle exposures, reporting odds ratios (ORs) and 95% confidence intervals [CIs], by ethnicity, for overall B-NHL and subtypes.</p><p>Results</p><p>We recruited 823 cases and 808 healthy controls. Among 307 PA/516 IJ B-NHL cases (mean age at diagnosis = 51 [±17] versus 60 [±15] years, respectively) subtype distributions differed, with diffuse large B-cell lymphoma (DLBCL) being prominent among PA (71%) compared to IJ (41%); follicular lymphoma (FL), was observed in 14% versus 28%, and marginal zone lymphoma, in 2% versus 14%, respectively. Overall B-NHL in both populations was associated with recreational sun exposure OR = 1.43 [CI:1.07–1.91], black hair-dye use OR = 1.70 [CI:1.00–2.87], hospitalization for infection OR = 1.68 [CI:1.34–2.11], and first-degree relative with hematopoietic cancer, OR = 1.69 [CI:1.16–2.48]. An inverse association was noted with alcohol use, OR = 0.46 [CI:0.34–0.62]. Subtype-specific exposures included smoking (FL, OR = 1.46 [CI:1.01–2.11]) and >monthly indoor pesticide use (DLBCL, OR = 2.01 [CI:1.35–3.00]). Associations observed for overall B-NHL in PA only included: gardening OR = 1.93 [CI:1.39–2.70]; history of herpes, mononucleosis, rubella, blood transfusion (OR>2.5, P<0.01 for all); while for IJ risk factors included growing fruits and vegetables, OR = 1.87 [CI:1.11–3.15]; and self-reported autoimmune diseases, OR = 1.99 [CI:1.34–2.95].</p><p>Conclusions</p><p>In these geographically proximate populations we found some unique risk factors for B-NHL. Heterogeneity in the observed associations by ethnicity could reflect differences in lifestyle, medical systems, and reporting patterns, while variations by histology infer specific etiologic factors for lymphoma subtypes.</p></div

Life style exposures- Adjusted OR for B-NHL and subtypes, overall and by population^□.

<p>Lists the overall odds ratio (OR) with 95% confidence interval (CI) for all risk factors affecting overall B-cell non-Hodgkin lymphoma (B-NHL) and subtypes: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and marginal zone lymphoma (MZL), stratified by population (Jews, Arabs), frequency matched by sex and age categories (4 year groupings); adjusted for marital status, education (yrs), ethnic origin for Jews (Ashkenazi, North African, West Asian and Sephardic) and residential region for Arabs (North, South, Center, other). The columns list the exposure category and the OR. The colored grid indicates the OR associated with the exposure for each subtype separately. Red (blue) represents the exposure increases (decreases) risk. ^Xindicates an association with P<0.05, whereas ^XXindicates P<0.01. <i>m</i> indicates missing due to lack of data. <i>Int</i> indicates interaction between exposure and sub-populations P<0.05. ^□based on schema designed by Morton et al.</p