CD38 IS OVEREXPRESSED BY IMMUNE CELLS IN CUTANEOUS LUPUS SKIN
Bibliographic record
Abstract
O019 / #487 Topic: AS07 - Cutaneous Lupus ABSTRACT CONCURRENT SESSION 03: INNATE AND ADAPTIVE IMMUNITY IN SLE 22-05-2025 1:40 PM - 2:40 PM Background/Purpose Cutaneous lupus erythematosus (CLE) is an autoimmune skin disease in which metabolic abnormalities may drive immune dysregulation. An unbiased LC/MS metabolomics study showed dysregulation of nicotinamide adenine dinucleotide (NAD) metabolism in the skin of CLE patients compared to healthy controls. CD38 is a multifunctional transmembrane enzyme that plays an important role in NAD metabolism and has become an emerging therapeutic target in the treatment of systemic lupus erythematosus (SLE).[1] However, CD38 expression in CLE has not been well characterized. Methods We sought to investigate whether CD38 expression was altered in CLE lesional skin and identify the immune cell populations overexpressing CD38. Skin samples were obtained from CLE patients and normal controls seen at outpatient dermatology clinics at the University of Texas Southwestern Medical Center and Parkland Health. To compare the levels of CD38 expression between CLE vs normal skin, RNA levels were assessed by quantitative RT-PCR (qRT-PCR) from 16 CLE lesion skin biopsies and 11 control skin samples, and protein expression was assessed by immunohistochemistry on 7 CLE lesion skin biopsies and 4 control skin samples. Immunofluorescence double staining of CD38 with CD3, CD20, and CD68 was performed using 5 CLE lesion skin biopsies and 5 control skin samples to examine CD38 expression of candidate immune cell populations, including T cells (CD3), B cells (CD20), and monocytes (CD68), respectively. Manders’ coefficients M1 and M2 were determined to examine the extent of overlap between CD38 and CD3, CD20, and CD68 expression. Results qRT-PCR revealed a significant upregulation of CD38 expression in CLE patients vs controls (median log2 fold change of 6.56 vs -0.48, p<0.0001). Immunohistochemical staining of CD38 in 7 lesional and 4 normal skin samples revealed a significantly higher number of CD38 + cells in CLE skin (median: 2105.8 cells/mm2, IQR: 1164.9-2980.0) compared to normal skin (median: 238.5 cells/mm2, IQR: 181.5-426.8, p=0.02) (Figure 1). Immunofluorescence co-staining for CD38 revealed significantly increased CD3 + cells expressing CD38 in perifollicular regions (p<0.01) and CD68 + cells expressing CD38 in dermal-epidermal junctions (p<0.05) in CLE skin vs normal skin, whereas CD20 + cells were not demonstrated to have significantly increased CD38 expression (Figure 2). Figure 1 Figure 2 Conclusions qRT-PCR and immunohistochemical staining revealed that CD38 is significantly upregulated in lesional CLE skin, which supports our metabolomics data implying dysregulation of NAD + metabolism in CLE skin. In accordance with prior studies examining immune profiles of SLE,[2] immunofluorescence double staining demonstrated CD38 overexpression in a wide range of leukocytes, including T cells and monocytes. These findings support CD38 as a promising therapeutic target in patients with CLE. References: [1.] Ostendorf L. N Engl J Med 2020;383(12):1149-55. [2.] Burns M. Int J Mol Sci 2021;22(5):2424.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".