Biomarkers Associated with Organ-Specific Involvement in Juvenile Systemic Lupus Erythematosus

Greenan-Barrett, James; Doolan, Georgia; Shah, Devina; Virdee, Simrun; Robinson, George; Choida, Varvara; Gak, Nataliya; Gruijter, Nina de; Rosser, Elizabeth C.; Al-Obaidi, Muthana; Leandro, Maria; Zandi, Michael S; Pepper, Ruth J.; Salama, Alan D.; Jury, Elizabeth C.; Ciurtin, Coziana

doi:10.3390/ijms22147619

Cited by 15 publications

(12 citation statements)

References 237 publications

(427 reference statements)

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“…Therefore, the findings have limited applicability in JSLE. In addition, the complexity of the pathogenesis for JSLE suggests the need for research targeting young patients rather than adult patients [ 38 ]. In the present study, we aimed to investigate the lymphocyte subsets (CD4 + T cells, CD8 + T cells, γδ T cells, Tregs, CD19 + B cells, NK cells, and NKT cells) in JSLE patients and determine their associations with clinical phenotypes and disease activity, as well as long-term outcomes.…”

Section: Introductionmentioning

confidence: 99%

Associations of lymphocyte subpopulations with clinical phenotypes and long-term outcomes in juvenile-onset systemic lupus erythematosus

et al. 2022

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Objective Juvenile-onset systemic lupus erythematosus (JSLE) is a complex and heterogeneous immune-mediated disease. Cellular components have crucial roles in disease phenotypes and outcomes. We aimed to determine the associations of lymphocyte subsets with clinical manifestations and long-term outcomes in JSLE patients. Methods A cohort of 60 JSLE patients provided blood samples during active disease, of whom 34 provided further samples during inactive disease. In a longitudinal study, blood samples were obtained from 49 of the JSLE patients at 0, 3, and 6 months. The healthy control (HC) group consisted of 42 age-matched children. Lymphocyte subsets were analyzed by flow cytometry. Results The percentages of CD4+ T, γδ T, and NK cells were significantly decreased in JSLE patients compared with HC, while the percentages of CD8+ T, NKT, and CD19+ B cells were significantly increased. The percentage of regulatory T cells (Tregs) was significantly lower in JSLE patients with lupus nephritis (LN) than in non-LN JSLE patients and HC. The patients were stratified into high and low groups by the median frequency of each lymphocyte subset. The γδ T cells high group and NK cells high group were significantly related to mucosal ulcer. The CD4+ T cells high group was significantly associated with arthritis, and the NKT cells high group was substantially linked with autoimmune hemolytic anemia. The CD8+ T cells low group was mainly related to vasculitis, and the Tregs low group was significantly associated with LN. The percentage of Tregs was significantly increased at 6 months of follow-up, and the LN JSLE group had a lower Treg percentage than the non-LN JSLE group. Predictors of remission on therapy were high Tregs, high absolute lymphocyte count, direct Coombs test positivity, and LN absence at enrollment. Conclusion JSLE patients exhibited altered lymphocyte subsets, which were strongly associated with clinical phenotypes and long-term outcomes.

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Section: Introductionmentioning

confidence: 99%

Associations of lymphocyte subpopulations with clinical phenotypes and long-term outcomes in juvenile-onset systemic lupus erythematosus

et al. 2022

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“…Therefore, ORM has been studied as a potential blood biomarker for many diseases (28)(29)(30)(31). ORM has also been studied as a single or combined urinary biomarker of inflammatory diseases and cancer, including lupus nephritis, adult-onset Still's disease, psoriasis, rheumatoid arthritis, sepsis, Crohn's disease, bladder cancer, and hepatocellular carcinoma (32)(33)(34)(35)(36)(37)(38). In one cohort study, urinary ORM showed a significant association with incident hypertension at the 7-year follow-up (39).…”

Section: Discussionmentioning

confidence: 99%

Urinary proteome profiles associated with cognitive decline in community elderly residents—A pilot study

et al. 2023

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Non-invasive and simple methods enabling easy identification of individuals at high risk of cognitive decline are needed as preventive measures against dementia. This pilot study aimed to explore protein biomarkers that can predict cognitive decline using urine, which can be collected non-invasively. Study subjects were selected from participants in a cohort study of middle-aged and older community-dwelling adults who underwent cognitive testing using the Mini-Mental State Examination and provided spot urine samples at two time points with an interval of approximately 5 years. Seven participants whose cognitive function declined 4 or more points from baseline (Group D) and 7 sex- and age-matched participants whose cognitive function remained within the normal range during the same period (Group M) were selected. Urinary proteomics using mass spectrometry was performed and discriminant models were created using orthogonal partial least squares-discriminant analysis (OPLS-DA). OPLS-DA yielded two models that significantly discriminated between the two groups at baseline and follow-up. Both models had ORM1, ORM2, and SERPINA3 in common. A further OPLS-DA model using baseline ORM1, ORM2, and SERPINA3 data showed similar predictive performance for data at follow-up as it did for baseline data (sensitivity: 0.85, specificity: 0.85), with the receiver operating characteristic curve analysis yielding an area under the curve of 0.878. This prospective study demonstrated the potential for using urine to identify biomarkers of cognitive decline.

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“…Third, due to the retrospective study design, there was an absence of the British Isles Lupus Assessment group index (BILAG) or the Systemic Lupus International Collaborating Clinics damage index (SDI), genomic variants 26 and serological data, such as cytokines. 27 Appropriate advanced biomarkers 28…”

Section: Discussionmentioning

confidence: 99%

Autoantibody-based subgroups and longitudinal seroconversion in juvenile-onset systemic lupus erythematosus

et al. 2023

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ObjectiveTo explore the clinical value of autoantibody-based subgroup framework and the trend of autoantibody fluctuation in juvenile-onset SLE (JSLE).MethodsEighty-seven patients with JSLE were retrospectively collected and divided into subgroups via a two-step cluster based on the status of nine autoantibodies (double-stranded-DNA (dsDNA), nucleosome, histone, ribosomal P protein, Smith (Sm), u1-ribonucleoprotein (RNP), Sjögren’s syndrome antigen A (SSA)/Ro52, SSA/Ro60, Sjögren’s syndrome antigen B (SSB)/La). The final model selected in this study was based on adequate goodness of fit of the Silhouette coefficient and clinical interpretability. Clinical manifestations, organ involvements and disease activity were compared among the subgroups. Fluctuation in autoantibody status was also collected and analysed. Flare-free survival rates of the patients with positive/negative seroconversion and patients without seroconversion were studied by the Kaplan-Meier method and compared using a log-rank test.ResultsTwo clusters were identified: subgroup 1 (positive anti-Sm/RNP group) and subgroup 2 (negative anti-Sm/RNP group). There were more lupus nephritis (LN) and neuropsychiatric SLE (NPSLE) cases in subgroup 1 than in subgroup 2. Patients in subgroup 1 exhibited higher SLE Disease Activity Index scores compared with those in subgroup 2. Furthermore, anti-ribosomal P protein (61.1%), anti-nucleosome (58.3%) and anti-dsDNA (54%) were most commonly positive autoantibodies. A progressive decrease in the frequency of patients with positive results was demonstrated during the follow-up years. The decrease was notable for anti-dsDNA, anti-nucleosome and anti-ribosomal P protein (remaining 27.27%, 38.89% and 45.00% positive in the fifth year, respectively). While for those negative at baseline diagnosis, the decrease in the frequency of negative results was progressive but modest. Kaplan-Meier curve showed that the flare-free survival of patients with positive seroconversion was significantly lower than those without seroconversion and those with negative seroconversion (p<0.001).ConclusionsIn children with SLE, subgroups based on autoantibody profile can be applied to differentiate phenotypes and disease activity. Two important organ involvements, LN and NPSLE, are more common in patients with positive anti-Sm/RNP autoantibodies. Positive seroconversion may provide a valuable perspective for assessing flare, and it is worthwhile to retest the array of autoantibodies during follow-up.

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Biomarkers Associated with Organ-Specific Involvement in Juvenile Systemic Lupus Erythematosus

Cited by 15 publications

References 237 publications

Associations of lymphocyte subpopulations with clinical phenotypes and long-term outcomes in juvenile-onset systemic lupus erythematosus

Associations of lymphocyte subpopulations with clinical phenotypes and long-term outcomes in juvenile-onset systemic lupus erythematosus

Urinary proteome profiles associated with cognitive decline in community elderly residents—A pilot study

Autoantibody-based subgroups and longitudinal seroconversion in juvenile-onset systemic lupus erythematosus

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