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A histomorphometric analysis of synovial biopsies from individuals with Gulf War Veterans’ Illness and joint pain compared to normal and osteoarthritis synovium

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Abstract

We compared histologic, immunohistochemical, and vascular findings in synovial biopsies from individuals with Gulf War Veterans Illness and joint pain (GWVI) to findings in normal and osteoarthritis (OA) synovium. The following parameters were assessed in synovial biopsies from ten individuals with GWVI: lining thickness, histologic synovitis score, and vascular density in hematoxylin & eosin-stained sections; and CD68+ lining surface cells and CD15+, CD3+, CD8+, CD20+, CD38+, CD68+, and Ki-67+ subintimal cells and von Willebrand Factor+ vessels immunohistochemically. Comparisons were made to synovial specimens from healthy volunteers (n = 10) and patients with OA or RA (n = 25 each). Histologic appearance and quantitative assessments were nearly identical in the GWVI and normal specimens. Vascular density was between 25% (H & E stains; p = 0.003) and 31% (vWF immunostains; p = 0.02) lower in GWVI and normal specimens than in OA. CD68+ macrophages were the most common inflammatory cells in GWVI (45.3 ± 10.1 SEM cells/mm2) and normal synovium (45.6 ± 7.4) followed by CD3+ T cells (GWVI, 15.1 ± 6.3; normal, 27.1 ± 9.2), whereas there were practically no CD20+, CD38+, and CD15+ cells. All parameters except lining thickness and CD15 and CD20 expression were significantly higher in OA. Five (20%) OA specimens contained significant fractions of humoral immune cells in mononuclear infiltrates, although the overall differences in the relative composition of the OA mononuclear infiltrates did not reach statistical significance compared to GWVI and normal synovium. In summary, the GWVI and normal synovia were indistinguishable from each other and contained similar low-grade inflammatory cell populations consisting almost entirely of macrophages and T cells.

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Acknowledgments

We thank Gilda Clayburne for expert technical assistance, Irene Loglisci, Roxann Thompson, Valice Matthews, and John Romano (Philadelphia VA Medical Center, Department of Pathology) for help with histology, Alexis Ogdie (University of Pennsylvania School of Medicine) for assistance with data management, and Jasvinder Singh (University of Minnesota, Div. of Rheumatology) for helpful discussion and critical reading of the manuscript. F. Pessler was supported by National Institutes of Health Training Grants T32-AR 007442 and T32-CA 09140 and a 2007-8 American College of Rheumatology/Research and Education Foundation Amgen Pediatric Rheumatology Research Award.

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Authors and Affiliations

  1. Division of Rheumatology, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    F. Pessler

  2. Department of Rheumatology, Second Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

    L. Dai

  3. Division of Rheumatology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA

    L. X. Chen, C. Diaz-Torne, N. Çakir & H. R. Schumacher

  4. Division of Rheumatology, Philadelphia VA Medical Center, Philadelphia, PA, USA

    L. X. Chen & H. R. Schumacher

  5. Department of Rheumatology, Hospital Universitari de Belvitge, Barcelona, Spain

    C. Gomez-Vaquero

  6. Unit of Rheumatology, Hospital de la Santa Creu I Sant Pau, Barcelona, Spain

    C. Diaz-Torne

  7. Department of Pathology, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    M. E. Paessler

  8. Department of Rheumatology, Hospital for Special Surgery, New York, NY, USA

    C. Scanzello

  9. Department of Pathology, Philadelphia VA Medical Center, Philadelphia, PA, USA

    E. Einhorn

  10. Klinik und Poliklinik für Kinder-und Jugendmedizin, Technische Universität Dresden, Dresden, Germany

    F. Pessler

Authors
  1. F. Pessler
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  2. L. X. Chen
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  3. L. Dai
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  4. C. Gomez-Vaquero
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  5. C. Diaz-Torne
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  6. M. E. Paessler
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  7. C. Scanzello
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  8. N. Çakir
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  9. E. Einhorn
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  10. H. R. Schumacher
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Correspondence to F. Pessler.

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Pessler, F., Chen, L.X., Dai, L. et al. A histomorphometric analysis of synovial biopsies from individuals with Gulf War Veterans’ Illness and joint pain compared to normal and osteoarthritis synovium. Clin Rheumatol 27, 1127–1134 (2008). https://doi.org/10.1007/s10067-008-0878-0

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  • DOI: https://doi.org/10.1007/s10067-008-0878-0

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