Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Jan 25:10:29.
doi: 10.3389/fimmu.2019.00029. eCollection 2019.

Circulating Pentraxin3-Specific B Cells Are Decreased in Lupus Nephritis

Mariele Gatto  1   2 , Annika Wiedemann  2 , Nadja Nomovi  2 , Karin Reiter  2 , Eva Schrezenmeier  3 , Thomas Rose  2 , Franziska Szelinski  2 , Andreia C Lino  4 , Sonia Valentino  5 , Anna Ghirardello  1 , Thomas Dörner  2 , Andrea Doria  1
Affiliations

Circulating Pentraxin3-Specific B Cells Are Decreased in Lupus Nephritis

Mariele Gatto et al. Front Immunol. .

Abstract

Background: Pentraxin3 (PTX3) is overexpressed in kidneys of patients developing lupus nephritis (LN). Active LN is associated with reduced anti-PTX3 antibodies. However, abnormalities of B cell differentiation against PTX3 have not been characterized in systemic lupus erythematosus (SLE). Objective: Characterization of PTX3-specific (PTX3+) B cells in peripheral blood of SLE patients with or without LN and healthy donors (HD). Patients and Methods: SLE patients without LN, biopsy-proven LN and matched HD were analyzed. Active LN was defined as proteinuria>0.5 g/day or CrCl<60 ml/min/1.73 m2 with active urinary sediment. Peripheral B cells were analyzed for direct PTX3 binding by flow cytometry using PTX3 labeled with cyanine 5 (Cy5) and phycoerythrin (PE). Results: Initially, a flow cytometry based assay to identify PTX3+ B cells was developed by demonstrating simultaneous binding of PTX3-Cy5 and PTX3-PE. Specificity of B cells was validated by blocking experiments using unlabeled PTX3. We could identify circulating PTX3+ B-cells in HD and patients. Notably, LN patients showed a significantly diminished number of PTX3+ B cells (SLE vs. LN p = 0.033; HD vs. LN p = 0.008). This decrease was identified in naïve and memory B cell compartments (naïve: SLE vs. LN p = 0.028; HD vs. LN p = 0.0001; memory: SLE vs. LN p = 0.038, HD vs. LN p = 0.011). Conclusions: Decreased PTX3+ B cells in LN within the naïve and memory compartment suggest their negative selection at early stages of B cell development potentially related to a decreased regulatory function. PTX3+ B cells could candidate for autoantigen-defined regulatory B cells as a striking abnormality of LN patients.

Keywords: PTX3+ B cells; SLE; biomarkers; flow-cytometry; lupus nephritis.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Identification of PTX3+ B cells among CD19+CD20+ B cells. (A) Three representative dot plots of the PTX3-specific B cells before and after blocking with unlabeled PTX3. Only B cells staining positive for both PTX3-Cy5 and PTX3-PE were considered (light gray square). (B) Quantification of PTX3 binding among B cells before and after blocking of PTX3. Cy5, cyanin 5; PE, phycoerythrin. ** < 0.01.
Figure 2
Figure 2
PTX3+ B cells are decreased in patients with lupus nephritis and are mainly confined to CD27−IgD+ B cells. (A) Absolute numbers of PTX3+ B cells (cell/mL) within (left) total; (middle) naïve or (right) memory B cells in HD (n = 22) and SLE (n = 26) and LN (n = 12) patients. (B) Frequencies of PTX3+ B cells (left), naïve (middle), and memory (right) are decreased in LN (n = 12) in comparison with HD (n = 22) and SLE (n = 26). (C) Distribution of CD27 and IgD expression by PTX3+ B cell subsets are shown. Enrichment in the naïve pool with decreases in the other subsets was found in HD (n = 22) and SLE (n = 26), but not in LN (n = 12). (D) Pie charts of percentages of PTX3+ CD27IgD subsets within the PTX3+ B cell pool are consistent with distribution of absolute numbers. Mann-Whitney U-test (* < 0.05, ** < 0.01, *** < 0.001). SLE, systemic lupus erythematosus; HD, healthy donors; LN, lupus nephritis; PTX3 pentraxin3.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

  • Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition).
    Cossarizza A, Chang HD, Radbruch A, Abrignani S, Addo R, Akdis M, Andrä I, Andreata F, Annunziato F, Arranz E, Bacher P, Bari S, Barnaba V, Barros-Martins J, Baumjohann D, Beccaria CG, Bernardo D, Boardman DA, Borger J, Böttcher C, Brockmann L, Burns M, Busch DH, Cameron G, Cammarata I, Cassotta A, Chang Y, Chirdo FG, Christakou E, Čičin-Šain L, Cook L, Corbett AJ, Cornelis R, Cosmi L, Davey MS, De Biasi S, De Simone G, Del Zotto G, Delacher M, Di Rosa F, Di Santo J, Diefenbach A, Dong J, Dörner T, Dress RJ, Dutertre CA, Eckle SBG, Eede P, Evrard M, Falk CS, Feuerer M, Fillatreau S, Fiz-Lopez A, Follo M, Foulds GA, Fröbel J, Gagliani N, Galletti G, Gangaev A, Garbi N, Garrote JA, Geginat J, Gherardin NA, Gibellini L, Ginhoux F, Godfrey DI, Gruarin P, Haftmann C, Hansmann L, Harpur CM, Hayday AC, Heine G, Hernández DC, Herrmann M, Hoelsken O, Huang Q, Huber S, Huber JE, Huehn J, Hundemer M, Hwang WYK, Iannacone M, Ivison SM, Jäck HM, Jani PK, Keller B, Kessler N, Ketelaars S, Knop L, Knopf J, Koay HF, Kobow K, Kriegsmann K, Kristyanto H, Krueger A, Kuehne JF, Kunze-Schumacher H, Kvistborg P, Kwok I, Latorre D, Lenz D, Levings MK, Lino AC, Liotta F, Long HM, Lugli E, MacDonald KN, M… See abstract for full author list ➔ Cossarizza A, et al. Eur J Immunol. 2021 Dec;51(12):2708-3145. doi: 10.1002/eji.202170126. Epub 2021 Dec 7. Eur J Immunol. 2021. PMID: 34910301 Free PMC article. Review.
  • Anti-pentraxin 3 antibodies and residual disease activity in rheumatoid arthritis.
    Salvato M, Frizzera F, Ghirardello A, Calligaro A, Botsios C, Zen M, Doria A, Giollo A. Salvato M, et al. Rheumatology (Oxford). 2025 Apr 1;64(4):1672-1678. doi: 10.1093/rheumatology/keae529. Rheumatology (Oxford). 2025. PMID: 39340807 Free PMC article.
  • Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition).
    Cossarizza A, Chang HD, Radbruch A, Acs A, Adam D, Adam-Klages S, Agace WW, Aghaeepour N, Akdis M, Allez M, Almeida LN, Alvisi G, Anderson G, Andrä I, Annunziato F, Anselmo A, Bacher P, Baldari CT, Bari S, Barnaba V, Barros-Martins J, Battistini L, Bauer W, Baumgart S, Baumgarth N, Baumjohann D, Baying B, Bebawy M, Becher B, Beisker W, Benes V, Beyaert R, Blanco A, Boardman DA, Bogdan C, Borger JG, Borsellino G, Boulais PE, Bradford JA, Brenner D, Brinkman RR, Brooks AES, Busch DH, Büscher M, Bushnell TP, Calzetti F, Cameron G, Cammarata I, Cao X, Cardell SL, Casola S, Cassatella MA, Cavani A, Celada A, Chatenoud L, Chattopadhyay PK, Chow S, Christakou E, Čičin-Šain L, Clerici M, Colombo FS, Cook L, Cooke A, Cooper AM, Corbett AJ, Cosma A, Cosmi L, Coulie PG, Cumano A, Cvetkovic L, Dang VD, Dang-Heine C, Davey MS, Davies D, De Biasi S, Del Zotto G, Dela Cruz GV, Delacher M, Della Bella S, Dellabona P, Deniz G, Dessing M, Di Santo JP, Diefenbach A, Dieli F, Dolf A, Dörner T, Dress RJ, Dudziak D, Dustin M, Dutertre CA, Ebner F, Eckle SBG, Edinger M, Eede P, Ehrhardt GRA, Eich M, Engel P, Engelhardt B, Erdei A, Esser C, Everts B, Evrard M, Falk CS, Fehniger TA, Felipo-Benavent M, Fer… See abstract for full author list ➔ Cossarizza A, et al. Eur J Immunol. 2019 Oct;49(10):1457-1973. doi: 10.1002/eji.201970107. Eur J Immunol. 2019. PMID: 31633216 Free PMC article.
  • Phosphatidylcholine-specific B cells are enriched among atypical CD11chigh and CD21low memory B cells in antiphospholipid syndrome.
    Nitschke E, Dang VD, Rincon-Arevalo H, Szelinski F, Ritter J, Schrezenmeier E, Alexander T, Le TA, Chen Y, Wiedemann A, Gonzalez JB, Lino AC, Stefanski AL, Dörner T. Nitschke E, et al. Front Immunol. 2025 Jun 3;16:1585953. doi: 10.3389/fimmu.2025.1585953. eCollection 2025. Front Immunol. 2025. PMID: 40529352 Free PMC article.

References

    1. Doria A, Iaccarino L, Ghirardello A, Zampieri S, Arienti S, Sarzi-Puttini P, et al. . Long-term prognosis and causes of death in systemic lupus erythematosus. Am J Med. (2006) 119:700–6. 10.1016/j.amjmed.2005.11.034 - DOI - PubMed
    1. Hanly JG, Su L, Urowitz MB, Romero-Diaz J, Gordon C, Bae SC, et al. . A longitudinal analysis of outcomes of lupus nephritis in an international inception cohort using a multistate model approach. Arthritis Rheumatol. (2016) 68:1932–44. 10.1002/art.39674 - DOI - PMC - PubMed
    1. Moroni G, Vercelloni PG, Quaglini S, Gatto M, Gianfreda D, Sacchi L, et al. . Changing patterns in clinical-histological presentation and renal outcome over the last five decades in a cohort of 499 patients with lupus nephritis. Ann Rheum Dis. (2018) 77:1318–25. 10.1136/annrheumdis-2017-212732 - DOI - PubMed
    1. Gatto M, Iaccarino L, Ghirardello A, Punzi L, Doria A. Clinical and pathologic considerations of the qualitative and quantitative aspects of lupus nephritogenic autoantibodies: a comprehensive review. J Autoimmun. (2016) 69:1–11. 10.1016/j.jaut.2016.02.003 - DOI - PubMed
    1. Doria A, Gatto M. Nephritogenic-antinephritogenic antibody network in lupus glomerulonephritis. Lupus (2012) 21:1492–6. 10.1177/0961203312462267 - DOI - PubMed

Publication types

MeSH terms