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IgM on the surface of T cells: a novel biomarker of pediatric-onset systemic lupus erythematosus

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Abstract

Background

Children with systemic lupus erythematosus (SLE) frequently have kidney involvement. Lupus nephritis sometimes presents alone, without systemic SLE features, representing the so-called full-house nephropathy (FHN). Distinguishing patients with SLE or FHN has therapeutic and prognostic implications.

Methods

In this retrospective observational study, we determined the presence of IgM on the surface of T cells (T cell IgM) by flow cytometry and characterized its ability in distinguishing SLE and FHN patients in a large pediatric cohort (n = 84). Fifty-seven patients with SLE (≥ 4 SLICC criteria at disease onset or during the follow-up) and 27 patients with FHN (3 or less SLICC criteria) were enrolled.

Results

Elevated T cell IgM levels were found in 24/25 SLE patients in active phase of disease and in 29/45 SLE patients in remission. In contrast, among FHN patients, only 1/9 presented this characteristic in active phase of disease and 0/20 in remission. Compared with standardized SLICC laboratory parameters, i.e., autoantibody titers and hypocomplementemia, T cell IgM positivity showed an extremely high sensitivity and specificity for the diagnosis of SLE, with the highest area under the curve (0.97, p < 0.001) by receiver operating characteristic analysis, similar to ANA (0.96, p < 0.001) and anti-dsDNA (0.90, p < 0.001) autoantibodies.

Conclusions

Altogether, our data indicate that T cell IgM intensity may be a useful tool to correctly classify patients with lupus nephritis as SLE or FHN since disease onset.

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Funding

M.C. and M.V. were supported by Associazione per la Cura del Bambino Nefropatico-Onlus and Ricerca Corrente of the Italian Ministry of Health.

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Authors and Affiliations

  1. Renal Diseases Research Unit, Genetics and Rare Diseases Research Area, Bambino Gesù Children’s Hospital, IRCCS, Viale S. Paolo 15, 00146, Rome, Italy

    Manuela Colucci

  2. Division of Nephrology, Department of Pediatric Subspecialties, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy

    Barbara Ruggiero, Alessandra Gianviti, Francesco Emma & Marina Vivarelli

  3. B Cell Pathophysiology Unit, Immunology Research Area, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy

    Maria Manuela Rosado & Rita Carsetti

  4. Division of Rheumatology, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy

    Claudia Bracaglia & Fabrizio De Benedetti

Authors
  1. Manuela Colucci
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  2. Barbara Ruggiero
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  3. Alessandra Gianviti
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  4. Maria Manuela Rosado
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  5. Rita Carsetti
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  6. Claudia Bracaglia
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  7. Fabrizio De Benedetti
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  8. Francesco Emma
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  9. Marina Vivarelli
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Contributions

M.C. designed and performed experiments, data analysis, and manuscript preparation; M.M.R. helped with experiments, data interpretation, and manuscript preparation; B.R., A. G., R.C., C.B., F.D.B., F.E., and M.V. helped with study design, data interpretation, and manuscript preparation. All authors approved the final version of the manuscript.

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Correspondence to Manuela Colucci.

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The authors declare that they have no competing interests.

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This study was performed following Bambino Gesù Children’s Hospital, IRCCS institutional guidelines, with approval from local Ethics Committee and in compliance with the declaration of Helsinki.

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Figure S1

Patient study flowchart. Of the 84 enrolled patients with clinical suspicion of SLE or isolated lupus nephritis (LN), 57 fulfilled SLE criteria according to the SLICC classification, and 27 did not. All the patients with kidney involvement, except 2 SLE patients, were subjected to kidney biopsy. Of the 17 SLE patients without LN at disease onset, 2 patients developed LN during the follow-up. Three of the 27 patients with isolated biopsy-proven LN had ANA and or anti-dsDNA positivity, fulfilling the “stand-alone renal” criteria based on SLICC classification. All other isolated LN patients without ANA and/or anti-dsDNA positivity were defined as “full-house” nephropathy (FHN) patients. Of these, one patient developed several other SLE criteria during the follow-up. *, kidney biopsy was not performed in 2 SLE patients despite the renal involvement (TIFF 318 kb).

High Resolution Image (PNG 1326 kb)

Figure S2

Gating strategy for flow cytometry analysis. PBMCs isolated by density gradient centrifugation were stained with fluorochrome-conjugated antibodies to CD5, CD19, and IgM and then analyzed by flow cytometry. IgM mean fluorescence intensity (indicated in the histogram panels) was determined in gated CD19-CD5+ T cells, as previously described [16]. One representative FHN patient and one representative SLE patient are depicted (TIFF 311 kb)

High Resolution Image (PNG 1230 kb)

Figure S3

Analysis of T cell IgM intensity in the same SLE patients in active (onset or relapse) or inactive (remission) phase of disease. PBMCs isolated from the same patients (n = 11) in two different phases of disease were analyzed for their T cell IgM intensity by flow cytometry. Dotted line represents the normal cut-off. Horizontal lines indicate the medians and statistical significance was determined using the Wilcoxon signed-rank test (TIFF 187 kb)

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Colucci, M., Ruggiero, B., Gianviti, A. et al. IgM on the surface of T cells: a novel biomarker of pediatric-onset systemic lupus erythematosus. Pediatr Nephrol 36, 909–916 (2021). https://doi.org/10.1007/s00467-020-04761-7

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  • DOI: https://doi.org/10.1007/s00467-020-04761-7

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