All ETDs from UAB

Advisory Committee Chair

Elliot J Lefkowitz

Advisory Committee Members

Devin M Absher

Elizabeth E Brown

Sara J Cooper

Brittany N Lasseigne

Richard M Myers

Document Type

Dissertation

Date of Award

2023

Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine

Abstract

Autoimmune diseases are a classification of more than eighty diseases where the immune system recognizes a self-antigen and mistakenly attacks the body’s own tissue, inducing inflammation a nd p otentially l eading t o d amage. Autoimmune diseases disproportionately affect women and develop at any age depending on the disease. The prevalence of some autoimmune diseases is increased in minority populations. Despite this, research into higher-risk populations is lacking. This highlights the need to contribute research into understanding autoimmune disease pathogenesis in diverse studies to understand why disease is more severe in these populations. We analyzed transcriptomes and methylomes of classical monocytes from self-reported African American (AA) systemic sclerosis (SSc) patients to identify whether there were different pathways involved in disease development when compared to self-reported European American (EA) SSc patients. Next, we conducted a genome-wide methylation study on buffy c oat s amples c omparing the methylomes of AA systemic lupus erythematosus (SLE) patients to EA SLE patients with LN. Genotyping data was also incorporated to detect ancestry-specific differences c ontributing t o differential me thylation. We th en pe rformed a singlecell multiomics method on healthy donor PBMCs to measure cell surface proteins that can potentially identify immune cell subtypes carrying the SLE-associated IFN hypomethylation signature. Mitochondrial DNA mutations were also analyzed for tracing clonality between common immune cell lineages. In the SSc study, we found differentially methylated s ites n ear g enes involved in metabolic processes which contrasts with similar studies conducted on iii mostly EA patients. Next, in the SLE study, we found that EA SLE patients with LN exhibited a similar methylation profile as AA SLE patients with and without LN which differs from previous studies showing this signature primarily in AA SLE patients. While experimenting with single-cell multiomics, we found that in PBMCs the surface protein modality correlated with the two other modalities and mtDNA could be used to infer lineage in both the lymphoid and myeloid populations.

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