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Multicenter Study
. 2025 May 1;64(5):2676-2687.
doi: 10.1093/rheumatology/keae559.

Soluble urine activated leukocyte cell adhesion molecule is a strong predictor of lupus nephritis

Dalena Chu  1 , Noa Schwartz  2 , Jeanette Ampudia  1 , Joel Guthridge  3 , Judith James  3 , Jill P Buyon  4 , Stephen Connelly  1 , Maple Fung  1 , Cherie T Ng  1 ; Accelerating Medicines Partnership: RA/SLE Network; Andrea Fava  5 , Michelle Petri  5 , Chandra Mohan  6 , Chaim Putterman  2   7   8
Collaborators, Affiliations
Multicenter Study

Soluble urine activated leukocyte cell adhesion molecule is a strong predictor of lupus nephritis

Dalena Chu et al. Rheumatology (Oxford). .

Abstract

Objectives: To evaluate urinary activated leucocyte cell adhesion molecule (ALCAM) and CD6 as predictors of LN progression or disease resolution across a 1-year study.

Methods: Serum and urine samples from biopsy proven LN subjects (n = 122) were prospectively collected over the course of a year at 3- or 6-month intervals (weeks 0, 12, 26 and 52) across multiple study sites and assessed for soluble ALCAM and CD6 levels. Urine creatinine from the same urine sample was used to normalize the levels of urinary ALCAM and urinary CD6. Measured levels of serum and urine ALCAM and CD6 were then analysed against disease metrics cross-sectionally and longitudinally.

Results: Cross-sectional analysis at baseline revealed that urinary ALCAM significantly correlated with urine protein creatinine ratio, renal SLEDAI, and the Physician Global Assessment (PGA), and negatively correlated with serum C3 and C4. Receiver operating characteristic curve analysis demonstrated that urinary ALCAM is a predictor of LN with an area under the curve (AUC) of 0.97, compared with urinary CD6 with an AUC of 0.71. Importantly, the change in urinary ALCAM over a 3-month period distinguished between non-responders and responders at week 52.

Conclusion: Urinary ALCAM is reflective of changes in LN and may be predictive of response status.

Keywords: ALCAM; CD6; lupus nephritis; urine biomarkers.

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Figures

Figure 1.
Figure 1.
uALCAM is elevated in LN. (A and D) uALCAM (labelled as ALCAM), sALCAM and uCD6 (labelled as CD6) are elevated in LN. (B) Correlation of uALCAM and sALCAM at V0. (C) uALCAM decreases while sALCAM remains relatively stable. (E) uALCAM is elevated in mixed LN (n = 58) relative to early-stage disease (n = 33) and proliferative LN (n = 88). (F) No differences were observed with uCD6. (G) UPCR is elevated in mixed LN (n = 57) and membranous LN (n = 60) relative to early-stage disease (n = 30). (H–J) Correlation plots between uALCAM, uCD6 and UPCR with the activity and chronicity indices. (K and L) Percentage of cells positive for ADAM17 (K) and ALCAM (L) between controls and LN. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. ADAM17: a disintegrin and metalloproteinase 17; ALCAM: activated leucocyte cell adhesion molecule; LN: lupus nephritis; s: serum; u: urinary; UPCR: urine protein creatinine ratio
Figure 2.
Figure 2.
Urinary ALCAM and CD6 trends longitudinally with LN. Subjects with a urine baseline sample and at least two follow-up samples were included in a longitudinal analysis where urinary ALCAM and CD6 were analysed against measures of LN including (A) UPCR, (B) renal SLEDAI, (C) C3, and (D) C4 complement proteins. Both urinary ALCAM and CD6 trends with UPCR and renal SLEDAI while there is an inverse relationship between urinary ALCAM and CD6 with C3 and C4. The number of available subjects is indicated above each visit. Datapoints denote mean, and bars denote standard error. ALCAM: activated leucocyte cell adhesion molecule; LN: lupus nephritis; UPCR: urine protein creatinine ratio
Figure 3.
Figure 3.
Urinary ALCAM correlates with disease parameters and is associated with UPCR. (A–D) uALCAM correlated with UPCR (P < 0.0001) (A) and renal SLEDAI (P < 0.0001) (B); uCD6 did not correlate with UPCR (P = 0.36) (C) nor renal SLEDAI (P = 0.054) (D) as determined by Spearman’s rank correlation. (E) Receiver operating characteristic (ROC) curve shows that uALCAM (left) is a better predictor of active LN compared with uCD6 (right). (F) A mixed model for repeated measures was used to observe the patterns of change in UPCR and their associations with fixed effects. The fit of the model revealed that uALCAM (P < 0.0001) at baseline significantly associated with UPCR. Values highlighted in bold indicate statistical significance (P < 0.05). ALCAM: activated leucocyte cell adhesion molecule; DF: degrees of freedom; LN: lupus nephritis; UPCR: urine protein creatinine ratio; pr: proteinuria
Figure 4.
Figure 4.
Urinary ALCAM correlates with LN indicators. The relationship between UPCR with the Physician Global Assessment (PGA), C3 and C4 complement proteins, and dsDNA was assessed and compared with that of urinary ALCAM. (A) Both UPCR and urinary ALCAM significantly correlated with PGA. (B and C) No correlations between UPCR and C3 or UPCR and C4 were detected while urinary ALCAM negatively correlated with both C3 and C4 complement proteins. (D) Neither UPCR nor urinary ALCAM correlated with anti-dsDNA antibody levels. Correlations determined by Spearman’s rank correlation. Values highlighted in bold indicate statistical significance (P < 0.05). ALCAM: activated leucocyte cell adhesion molecule; LN: lupus nephritis; UPCR: urine protein creatinine ratio
Figure 5.
Figure 5.
Reductions in urinary ALCAM is predictive of response status. (A and B) Schematic illustration of the 3-month intervals evaluated. (C) A change in urinary ALCAM between weeks 0 and 12 distinguished NR from PR (P < 0.01) and CR (P < 0.05). (D) A change in UPCR between weeks 0 and 12 distinguished NR from CR (P < 0.05). (E) A change in urinary ALCAM between weeks 12 and 26 distinguished NR from PR (P < 0.001). (F) A change in UPCR between weeks 12 and 26 did not distinguish amongst response statuses. One-way ANOVA with multiple comparisons. (G) CR experienced a decrease in urinary ALCAM over the course of the 1-year study. *P < 0.05, **P < 0.01, ***P < 0.001. ALCAM: activated leucocyte cell adhesion molecule; CR: complete response; LN: lupus nephritis; NR: no response; PR: partial response; UPCR: urine protein creatinine ratio
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References

    1. Anders HJ, Saxena R, Zhao MH et al. Lupus nephritis. Nat Rev Dis Primers 2020;6:7. - PubMed
    1. Moroni G, Depetri F, Ponticelli C. Lupus nephritis: when and how often to biopsy and what does it mean? J Autoimmun 2016;74:27–40. - PubMed
    1. Kernder A, Richter JG, Fischer-Betz R et al. Delayed diagnosis adversely affects outcome in systemic lupus erythematosus: cross sectional analysis of the LuLa cohort. Lupus 2021;30:431–8. - PMC - PubMed
    1. Chalmers SA, Ayilam Ramachandran R, Garcia SJ et al. The CD6/ALCAM pathway promotes lupus nephritis via T cell-mediated responses. J Clin Invest 2022;132:147334. - PMC - PubMed
    1. Chalmers S, Garcia S, Ampudia J, Ng C, Connelly S, Putterman C, eds. Amelioration of immune complex-mediated glomerulonephritis by CD6 modulation. Atlanta, GA: ACR, 2019.

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