Genetic load in incomplete lupus erythematosus

Matt Slief; Joseph M Kheir; Miles Smith; Colin Mowery; Susan Macwana; Wade DeJager; Catriona A Wagner; Teresa Aberle; Judith A James; Joel M Guthridge

doi:10.1136/lupus-2022-000843

Genetic load in incomplete lupus erythematosus

Lupus Sci Med. 2023 Jan;10(1):e000843. doi: 10.1136/lupus-2022-000843.

Authors

Matt Slief^{1

2}, Joseph M Kheir¹, Miles Smith¹, Colin Mowery¹, Susan Macwana¹, Wade DeJager¹, Catriona A Wagner¹, Teresa Aberle¹, Judith A James^{1

3}, Joel M Guthridge^{4

3}

Affiliations

¹ Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
² College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
³ Department of Medicine, Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
⁴ Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA Joel-Guthridge@omrf.org.

Abstract

Objective: Patients with incomplete lupus erythematosus (ILE) have lupus features but insufficient criteria for SLE classification. Some patients with ILE transition to SLE, but most avoid major organ involvement. This study tested whether the milder disease course in ILE is influenced by reduced SLE risk allele genetic load.

Methods: We calculated the genetic load based on 99 SLE-associated risk alleles in European American patients with SLE (≥4 American College of Rheumatology (ACR) 1997 criteria, n=170), patients with ILE (3 ACR 1997 criteria, n=169), a subset of patients with ILE not meeting Systemic Lupus International Collaborating Clinics (SLICC) classification (ILE^SLICC, n=119) and healthy controls (n=133). Unweighted genetic loads were calculated as the total sum of risk alleles for each individual, while weighted genetic loads were defined as the sum of risk alleles multiplied by the natural logarithm of the previously published OR of each risk allele for SLE susceptibility.

Results: The median unweighted and weighted SLE risk allele genetic load was significantly greater in patients with ILE (unweighted: 81, p value=0.01; weighted: 16.3, p value=0.001) and patients with SLE (80, p value=0.02; 16.29, p value=0.0006) compared with healthy controls (78, 15.76). Patients with ILE^SLICC trended towards an increased genetic load, although not statistically significant (unweighted: 80, p value=0.14; weighted: 16.05, p value=0.07). However, the median genetic load did not significantly differ between ILE and SLE, and genetic load did not differentiate patients with ILE and SLE (area under the curve=0.51, p=0.78) by receiver operator characteristic analysis.

Conclusions: Patients with ILE and SLE have comparable genetic loads of SLE risk loci, suggesting similar genetic predispositions between these conditions. Phenotypical differences between SLE and ILE may instead be influenced by ILE-specific variants and gene-environment interactions.

Keywords: Autoimmune Diseases; Polymorphism, Genetic; Systemic Lupus Erythematosus.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Disease Progression
Genetic Load
Humans
Lupus Erythematosus, Systemic* / genetics
Rheumatology*
Severity of Illness Index
United States

Abstract

Publication types

MeSH terms

Grants and funding