Date of Award

January 2024

Document Type

Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Natalia Neparidze

Abstract

Monoclonal gammopathy (MG) encompasses a spectrum of related diseases, with monoclonal gammopathy of undetermined significance (MGUS) being the most prevalent, serving as a precursor of smoldering and clinical multiple myeloma. While the association between gammopathies, metabolic conditions and antigenic stimulation has long been recognized, the precise mechanism remains unclear. Prior research has shown that a subset of MGUS and MM is driven by chronic antigenic stimulation of B cells by endogenous lipids and exogenous microbial antigens. The aim of this study is to assess the prevalence of metabolic comorbidities and viral infections in a large population with monoclonal gammopathy, providing insights into the disease’s pathophysiology and potential targets for intervention.

We conducted a retrospective chart review at a single center for patients aged 18 years and older, diagnosed with monoclonal gammopathy between 2014 and 2020 at Yale Cancer Center. We excluded patients without documented immunofixation or serum protein electrophoresis studies, as well as those with “faint” or “extremely faint’’ monoclonal components, resulting in a final data set of 1515 patients. Variables of interest including age, race, ethnicity, gender, dyslipidemia, diabetes, BMI, HIV, human papillomavirus (HPV), hepatitis C (HCV) and hepatitis B (HBV) status were identified by a combination of direct extraction from the EMR by the Joint Data Analytics Team and manual review of laboratory values, provider notes and scanned documents.

Among the 1515 patients diagnosed with monoclonal gammopathy, the average age was 76.36 (95% CI +/-11.3) years. The majority of patients (79.4%) self-identified as White, while 238 (15.7%) identified as Black/African American and 10 (0.7%) as Asian. Non-Hispanic individuals accounted for 1428 (94.3%) of the patients. The mean body mass index (BMI) was 27.5 (+/-6.73) years. Diabetes mellitus was reported in 614 (40.5%) cases, and hyperlipidemia was observed in 1362 (89.9%) cases. A total of 1236 (81.6%) patients used a statin at some point. When compared to a general adult U.S. population, dyslipidemia and diabetes were significantly more prevalent in our MGUS cohort (dyslipidemia prevalence 89.9% vs. 32.54%, p < 0.0001. Diabetes prevalence 40.5% vs. 14.3%, p < 0.0001). When looking at the specific lipid abnormalities driving this difference, we found that the prevalence of elevated serum triglycerides and total cholesterol was significantly higher than a general adult U.S. population (elevated triglycerides 35.8% vs. 15.9%, p < 0.0001, OR 2.843 with 95% CI 2.493 to 3.240. Elevated total cholesterol 32.5% vs. 29.07%, p = 0.0063, OR 1.176 with 95% CI 1.046 to 1.323). In our cohort, viral comorbidities included HIV in 20 patients (1.3%), which was significantly higher than the general adult U.S. population (1.3% vs. 0.55%, p = 0.0015). Additionally, 49 out of 812 (6%) patients tested positive for HCV, which was also significantly higher than the general population (6.0% vs. 1.1%, p < 0.0001). 56 of 711 (7.9%) patients had HBV infections. As of May 2023, out of the total 1515 patients, 485 (32%) deaths were reported.

Patients with MGUS demonstrate significantly higher rates of dyslipidemia, diabetes, HIV, and HCV compared to the general U.S. adult population. These findings highlight the importance of metabolic and viral infections in MG and emphasize the need for additional research on biologic drivers to guide preventative strategies. These findings also highlight the importance of metabolic conditions and viral infections as sources of chronic antigenic stimulation, acting as potential etiologic factors in the pathogenesis of monoclonal gammopathies. Our results emphasize the need for additional research on biologic drivers to guide preventative strategies for gammopathies. Correlative studies examining the metabolic profiles of the patients with monoclonal gammopathy are currently underway.

Comments

This thesis is restricted to Yale network users only. It will be made publicly available on 04/30/2026

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