Background: Lupus Nephritis (LN) is a severe complication of Systemic Lupus Erythematosus (SLE), significantly contributing to the morbidity and mortality of affected individuals. More than 60% of Latin American patients with SLE will develop LN, and 10% to 20% of these cases will progress to End-Stage Renal Disease [1, 2]. Recently, a newly described population of T lymphocytes known as peripheral helper T cells (Tph) [3] has been associated with autoimmune diseases and SLE [4]. This study explores the association between Tph cell percentages in the peripheral blood of systemic lupus erythematosus (SLE) patients—both with and without lupus nephritis (LN)—and renal biopsy classifications in LN patients, along with their activity and chronicity indices.

Objectives: To associate the circulating Tph cells with SLE and LN in relation to the histopathological classes, as well as the activity and chronicity indices of the disease in renal biopsies of LN patients.

Methods: Peripheral blood samples and renal biopsies from patients with SLE, LN and Healthy Controls (HC) were studied. Peripheral blood samples were subjected to density gradient separation and analyzed by flow cytometry, with surface markers established for Tph cells: T CD4+ CXCR5-PD1High. The renal tissue obtained by percutaneous procedure was analyzed through standard stained and direct immunofluorescence for IgG, IgA, IgM, C1q and C4c, posteriorly was classified according to the classes proposed by 2018 ISN/RPS classification by an expert nephropatologist. Descriptive analysis was used to determine means, frequencies, and interquartile ranges. The Shapiro-Wilk test was used to assess the data distribution, and the Mann-Whitney U test, Kruskal-Wallis test, and Dunn’s post hoc test were employed to compare the groups. Correlation analysis was performed using Spearman’s correlation coefficient. A p-value of ≤ 0.05 was considered statistically significant.

Results: Demographic Features Percentage of Tph Cells in Patients with SLE and HC Subjects

We studied 40 patients with SLE and 30 healthy controls (HC). The percentage of T helper (Tph) cells was significantly higher in SLE patients compared to HC, with a statistical difference [29.85% (p25 23.1%–p75 37.83%) vs 11.5% (p25 8.29–p75 15.15), p<0.001].

Tph Subpopulations CCR2+, CCR5+, and CCR2+/CCR5+ in Patients with SLE and Control Subjects

Subsequently, the Tph subpopulations expressing CCR2, CCR5, and both markers (CCR2/CCR5) on their membrane were analyzed. In the comparison between SLE patients and HC, only the Tph CCR5+ [13.05% (p25 8.08–p75 25.50) vs 8.61% (p25 6.69–p75 12.23); p=0.0135] and Tph CCR2+CCR5+ [22.0% (p25 15.18–p75 28.75) vs 27.65% (p25 21.33–p75 33.73); p=0.0126] showed statistically significant differences.

Tph Subpopulations in SLE Patients with and without LN.

On the other hand, we compare the Tph subpopulation between SLE patients with and without LN. The distribution of these subpopulation cells was similar in both groups (LN 31.59% (p25 22.95–p75 40) vs non-LN (30% (p25 23.1–p75 36.9), p=0.5501].

Circulating Tph Subpopulations according to LN classes

Ten renal biopsies from LN patients were obtained, 9 female patients and 1 male patient, with a mean age of 34.6 ± 11.56 years. The media of SLEDAI 2K was 12 ± 8 points. The ISN/RPS classes were the following Class III (n=2), Class IV (n=4), and Class IV/V (n=4). High-risk indices for progression to chronic kidney disease were classified as scores >12 in the activity index (22.22%, n=2) and >4 in the chronicity index (44.44%, n=4). There were 2 cases in which both indices indicated high risk (22.22%, n=2) and 1 case where both indices were categorized as low risk (11.11%, n=1). The Tph population by histopathological class was 41.75% (p25 40.9% - p75 42.6%)) for Class III, 41.03% (p25 40.1%-p75 41.7%) for Class IV, and 23.4% (p25 17.88% -p75 29.33%) for Class IV/V. Significant differences were found between Classes III and IV compared to Class IV/V (p=0.0074 and p=0.0049, respectively). The analysis according to CCR2+, CCR5+, and CCR2+CCR5+ expression in the subpopulation was performed. CCR2+ and CCR2+CCR5 showed a similar distribution according to LN classes (p>0.05). The CCR5+ expression have a trend to be higher in LN Class IV [25.7 (p25 17.6%–p75 26.4%) respect to Class IV/V [11.1% (p25 7.3%–p75 12.55%), however no statistical diference was found (p=0.0571). Activity and chronicity indices did not show significant differences in relation to Tph cells or any of the studied subpopulations.

Conclusion: The SLE patients have an increased number of Tph cells in patients with SLE compared to healthy controls (HC). Additionally, differences were found between chemokine receptor markers CCR2+ and CCR5+ between subjects with SLE and HC, with the subpopulation expressing isolated CCR5+ significantly increased in subjects with SLE, while the subpopulation with dual positive markers (CCR2+/CCR5+) was higher in HC. However, no differences were demonstrated between Tph subpopulations in SLE and LN. Subjects with LN showed a trend of increased CCR5+ positive subpopulation in proliferative Class III compared to mixed Class IV/V. No significant differences in Tph subpopulations were found based on activity or chronicity indices.

REFERENCES: NIL.

Acknowledgements: To our University for their support in the development of this work and for fostering our academic and professional growth.

Disclosure of Interests: None declared.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.