CD30 expression in autoimmune and inflammatory disorders

CD30 is expressed at high levels by activated cells in autoimmune and chronic inflammatory diseases. For example, both CD30-positive cells and the soluble form of CD30 (sCD30) are detectable in the circulation of some patients with rheumatoid arthritis (RA).1 In addition, sCD30 has been detected in the peripheral blood of patients with localized scleroderma2 and primary progressive multiple sclerosis.3 Upregulation of CD30 has also been detected on leukocytes in patients with systemic lupus erythematosus (SLE), atopic dermatitis (AD), asthma, allergic rhinitis and scleroderma (table).4 CD30-positive cells and/or high serum levels of sCD30 are particularly evident during the acute phase of these diseases.5 Therapy for asthma decreased CD30 expression on peripheral blood mononuclear cells derived from these patients.6 In general, high serum levels of sCD30 represent an independent predictor of disease progression and poor prognosis.4

Reported CD30 expression in immunologic diseases4
Disease sCD30 CD30+ cells
in blood
CD30+ cells
in tissues
Allergic rhinitis (N = 117) + mRNA +
Atopic asthma (N = 188) + + +
Atopic dermatitis (N = 499) + + +
Hashimoto thyroiditis (N = 3710) + - -
Primary biliary cirrhosis (N = 1311) + - +
Rheumatoid arthritis (N = 291) + - +
Scleroderma (N = 552) + - +
Sjögren syndrome (N = 112) + - +
SLE (N = 2113) + - +
Wegener granulomatosis (N = 5714) + - -

Adapted from Oflazoglu E, 2009

 

In a study in AD, there was strong expression of CD30 in a significant proportion of infiltrating T cells in lesional skin biopsies of patients with active disease. In contrast, virtually no CD30-positive cells were found in the skin of patients with acute contact dermatitis. CD30 expression directly correlated with the ability to produce IL-4 and IL-5, suggesting that CD30 expression may play a role in the pathogenesis of this disease.4,15 Serum sCD30 concentrations correlated with disease activity in patients with AD. This supports a role for CD30 as an activation marker, useful for evaluation of T-cell–driven immune responses.16

Serum levels of sCD30 doubled in patients with active SLE when compared to healthy controls.17 Likewise, serum levels of sCD30 were higher in active RA than in inactive RA and directly correlated with rheumatoid factor serum titers.1 Combined, these data support the involvement of CD30-positive T cells in immune processes and suggest there may be diagnostic value in measuring sCD30 levels in patients with autoimmune and inflammatory disorders.

References

  1. Gerli R, Muscat C, Bistoni O, et al. High levels of the soluble form of CD30 molecule in rheumatoid arthritis (RA) are expression of CD30+ T cell involvement in the inflamed joints. Clin Exp Immunol. 1995;102(3):547-550.
  2. Ihn H, Yazawa N, Kubo M, et al. Circulating levels of soluble CD30 are increased in patients with localized scleroderma and correlated with serological and clinical features of the disease. J Rheumatol. 2000;27(3):698-702.
  3. McMillan SA, McDonnell GV, Douglas JP, Hawkins SA. Evaluation of the clinical utility of cerebrospinal fluid (CSF) indices of inflammatory markers in multiple sclerosis. Acta Neurol Scand. 2000;101(4):239-243.
  4. Oflazoglu E, Grewal IS, Gerber H. Targeting CD30/CD30L in oncology and autoimmune and inflammatory diseases. In: Grewal IS, ed. Therapeutic Targets of the TNF Superfamily. In: Back N, Cohen IR, Lajtha A, Lambris JD, Paoletti R, eds. Advances in Experimental Medicine and Biology. Vol 647. New York, NY: Springer; 2009:174-185.
  5. Chiarle R, Podda A, Prolla G, Gong J, Thorbecke GJ, Inghirami G. CD30 in normal and neoplastic cells. Clin Immunol. 1999;90(2):157-164.
  6. Gourgiotis D, Papadopoulos NG, Bossios A, Zamanis P, Saxoni-Papageorgiou P. Immune modulator pidotimod decreases the in vitro expression of CD30 in peripheral blood mononuclear cells of atopic asthmatic and normal children. J Asthma. 2004;41(3):285-287.
  7. Suzuki H, Goto S, Ikeda K, Oshima T, Furukawa M, Takasaka T. IL-12 receptor β2 and CD30 expression in paranasal sinus mucosa of patients with chronic sinusitis. Eur Respir J. 1999;13(5):1008-1013.
  8. Leonard C, Tormey V, Faul J, Burke CM, Poulter LW. Allergen-induced CD30 expression on T cells of atopic asthmatics. Clin Exp Allergy. 1997;27(7):780-786.
  9. Bengtsson Å, Holm L, Bäck O, Fransson J, Scheynius A. Elevated serum levels of soluble CD30 in patients with atopic dermatitis (AD). Clin Exp Immunol. 1997;109(3):533-537.
  10. Okumura M, Hidaka Y, Kuroda S, Takeoka K, Tada H, Amino N. Increased serum concentration of soluble CD30 in patients with Graves’ disease and Hashimoto’s thyroiditis. J Clin Endocrinol Metab. 1997;82(6):1757-1760.
  11. Harada K-I, Tsuneyama K, Hiramatsu K, Nakanuma Y. Significance of CD30-positive lymphocytes in livers in primary biliary cirrhosis. J Gastroenterol Hepatol. 1999;14(12):1197-1202.
  12. Horie R, Ito K, Tatewaki M, et al. A variant CD30 protein lacking extracellular and transmembrane domains is induced in HL-60 by tetradecanoylphorbol acetate and is expressed in alveolar macrophages. Blood. 1996;88(7):2422-2432.
  13. Caligaris-Cappio F, Bertero MT, Converso M, et al. Circulating levels of soluble CD30, a marker of cells producing Th2-type cytokines, are increased in patients with systemic lupus erythematosus and correlate with disease activity. Clin Exp Rheumatol. 1995;13(3):339-343.
  14. Wang G, Hansen H, Tatsis E, Csernok E, Lemke H, Gross WL. High plasma levels of the soluble form of CD30 activation molecule reflect disease activity in patients with Wegener’s granulomatosis. Am J Med. 1997;102(6):517-523.
  15. Oflazoglu E, Simpson EL, Takiguchi R, Grewal IS, Hanifin JM, Gerber H-P. CD30 expression on CD1a+ and CD8+ cells in atopic dermatitis and correlation with disease severity. Eur J Dermatol. 2008;18(1):41-49.
  16. Caproni M, Bianchi B, D’Elios MM, De Carli M, Amedei A, Fabbri P. In vivo relevance of CD30 in atopic dermatitis. Allergy. 1997;52(11):1063-1070.
  17. Ciferská H, Horák P, Hermanová Z, et al. The levels of sCD30 and of sCD40L in a group of patients with systemic lupus erythematodes and their diagnostic value. Clin Rheumatol. 2007;26(5):723-728.