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Erythroid Disturbances Before and After Treatment of Portuguese Psoriasis Vulgaris Patients

A Cross-Sectional and Longitudinal Study

  • Original Research Article
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Abstract

Background: A few studies in psoriasis vulgaris patients have reported changes suggesting red blood cell (RBC) damage is linked to neutrophil activation, oxidative stress, and psoriasis worsening.

Objective: The aim of this study was to evaluate erythroid disturbances in Portuguese psoriasis vulgaris patients, before, during, and after treatment.

Methods: Across-sectional study (n = 73 patients vs 40 healthy control subjects) followed by a longitudinal study (n = 47 patients)was performed, with assessments before, and at 3, 6, and 12weeks of therapy (10 patients started topical treatment, 17 narrow-band UVB, and 20 photochemotherapy [psoralen plus UVA; PUVA]). Evaluations included hematologic data, total bilirubin levels,membrane-bound hemoglobin (MBH),membrane protein band 3 profile, total plasma antioxidant status (TAS), lipid peroxidation (thiobarbituric acid [TBA] assay), elastase, lactoferrin, and C-reactive protein (CRP).

Results: Before treatment, patients presented with higher leukocyte/neutrophil and reticulocyte counts, elastase, lactoferrin, TBA, TBA/TAS, reticulocyte production index, total bilirubin and MBH values, lower RBC and hematocrit, higher percentages of high-molecular-weight aggregates, and lower percentages of band 3 monomer. After treatment, we observed a reversal in most of the parameters. However, patients still presented with values suggestive of accelerated RBC damage, removal, and production, as most of the parameters were still higher than those in the control group; the same occurred with CRP.

Conclusion: Our data suggest that psoriasis vulgaris triggers an inflammatory response, with release of acutephase reactants, reactive oxygen species, cationic proteins, and proteases, leading to enhanced RBC damage/ aging and, ultimately, to enhanced RBC removal. These assumptions were strengthened by the observation that, with treatment, all of these changeswere reversed, the inflammation was reduced, the production of reticulocytes was increased, and the RBCs presented changes usually observed in younger/less damaged RBCs. These erythroid changes were enhanced with PUVA therapy, probably due to the more pronounced clearing of the lesions, as suggested by Psoriasis Area and Severity Index (PASI) scores. Finally, after treatment, a residual inflammation still persisted that might contribute to the observed erythroid disturbances.

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References

  1. Rocha-Pereira P, Santos-Silva A, Rebelo I, et al. The inflammatory response in mild and in severe psoriasis. Br J Dermatol 2004 May; 150 (5): 917–28

    Google Scholar 

  2. Krueger JG, Bowcock A. Psoriasis pathophysiology: current concepts of pathogenesis. Ann Rheum Dis 2005 Mar; 64 Suppl. 2: ii30–6

  3. Krueger G, Ellis CN. Psoriasis: recent advances in understanding its pathogenesis and treatment. J Am Acad Dermatol 2005 Jul; 53 (1 Suppl. 1): S94–100

    Google Scholar 

  4. Chowaniec O, Jablonska S, Beutner EH, et al. Earliest clinical and histological changes in psoriasis. Dermatologica 1981; 163 (1): 42–51

    Article  PubMed  CAS  Google Scholar 

  5. Orem A, Deger O, Cimsit G, et al. Plasma polymorphonuclear leukocyte elastase levels and its relation to disease activity in psoriasis. Clin Chim Acta 1997 Aug 8; 264 (1): 49–56

  6. Arican O, Aral M, Sasmaz S, et al. Serum levels of TNF-alpha, IFN-gamma, IL-6, IL-8, IL-12, IL-17, and IL-18 in patients with active psoriasis and correlation with disease severity. Mediators Inflamm 2005 Oct 24; 2005 (5): 273–9

  7. Scirica BM, Morrow DA. Is C-reactive protein an innocent bystander or proatherogenic culprit? The verdict is still out. Circulation 2006 May 2; 113 (17): 2128–34; discussion 51

  8. Yeh ET. CRP as a mediator of disease. Circulation 2004 Jun 1; 109 (21 Suppl. 1): II11–4

  9. Friedewald VE, Cather JC, Gelfand JM, et al. AJC editor’s consensus: psoriasis and coronary artery disease. Am J Cardiol 2008 Dec 15; 102 (12): 1631–43

  10. Friedewald Jr VE, Cather JC, Gordon KB, et al. The editor’s roundtable: psoriasis, inflammation, and coronary artery disease. Am J Cardiol 2008 Apr 15; 101 (8): 1119–26

  11. Pelle E, Mammone T, Maes D, et al. Keratinocytes act as a source of reactive oxygen species by transferring hydrogen peroxide to melanocytes. J Invest Dermatol 2005 Apr; 124 (4): 793–7

    Google Scholar 

  12. Rocha-Pereira P, Santos-Silva A, Rebelo I, et al. Erythrocyte damage in mild and severe psoriasis. Br J Dermatol 2004 Feb; 150 (2): 232–44

    Google Scholar 

  13. Setty AR, Curhan G, Choi HK. Obesity, waist circumference, weight change, and the risk of psoriasis in women: Nurses’ Health Study II. Arch Intern Med 2007 Aug 13-27; 167 (15): 1670–5

  14. Shirai K. Obesity as the core of the metabolic syndrome and the management of coronary heart disease. Curr Med Res Opin 2004 Mar; 20 (3): 295–304

  15. Sterry W, Strober BE, Menter A. Obesity in psoriasis: the metabolic, clinical and therapeutic implications. Report of an interdisciplinary conference and review. Br J Dermatol 2007 Oct; 157 (4): 649–55

    Google Scholar 

  16. Coimbra S, Oliveira H, Reis F, et al. Circulating levels of adiponectin, oxidized LDL and C-reactive protein in Portuguese patients with psoriasis vulgaris, according to body mass index, severity and duration of the disease. J Dermatol Sci 2009 Sep; 55 (3): 202–4

    Google Scholar 

  17. Panagiotakos DB, Pitsavos C, Yannakoulia M, et al. The implication of obesity and central fat on markers of chronic inflammation: the ATTICA study. Atherosclerosis 2005 Dec; 183 (2): 308–15

  18. Wellen KE, Hotamisligil GS. Obesity-induced inflammatory changes in adipose tissue. J Clin Invest 2003 Dec; 112 (12): 1785–8

    Google Scholar 

  19. Rao GM, Morghom LO. Effect of obesity on erythrocyte count and hemoglobin levels in Libyan diabetic patients. Clin Physiol Biochem 1986; 4 (4): 277–80

    PubMed  CAS  Google Scholar 

  20. Lutz HU. Erythocyte clearance. In: Harris J, editor. Blood cell biochemistry. New York (NY): Plenum Press, 1990: 81

    Google Scholar 

  21. Kay MM. Role of physiologic autoantibody in the removal of senescent human red cells. J Supramol Struct 1978; 9 (4): 555–67

    Article  PubMed  CAS  Google Scholar 

  22. Kay MM. Localization of senescent cell antigen on band 3. Proc Natl Acad Sci U S A 1984 Sep; 81 (18): 5753–7

  23. Kay MM, Goodman SR, Sorensen K, et al. Senescent cell antigen is immunologically related to band 3. Proc Natl Acad Sci U S A 1983 Mar; 80 (6): 1631–5

    Google Scholar 

  24. Bosman GJ, Werre JM, Willekens FL, et al. Erythrocyte ageing in vivo and in vitro: structural aspects and implications for transfusion. Transfus Med 2008 Dec; 18 (6): 335–47

    Google Scholar 

  25. Lutz HU, Bussolino F, Flepp R, et al. Naturally occurring anti-band-3 antibodies and complement together mediate phagocytosis of oxidatively stressed human erythrocytes. Proc Natl Acad Sci U S A 1987 Nov; 84 (21): 7368–72

    Google Scholar 

  26. Lutz HU. Naturally occurring anti-band 3 antibodies. Transfus Med Rev 1992 Jul; 6 (3): 201–11

  27. Low PS. Role of hemoglobin denaturation and band 3 clustering in initiating red cell removal. In: Magnani M, De Flora A, editors. Red blood cell aging. New York (NY): Plenum Press, 1991: 173–83

    Chapter  Google Scholar 

  28. Santos-Silva A, Rebelo MI, Castro EM, et al. Leukocyte activation, erythrocyte damage, lipid profile and oxidative stress imposed by high competition physical exercise in adolescents. in Chim Acta 2001 Apr; 306 (1-2): 119–26

  29. Santos-Silva A, Rebelo I, Castro E, et al. Erythrocyte damage and leukocyte activation in ischemic stroke. Clin Chim Acta 2002 Jun; 320 (1-2): 29–35

  30. Belo L, Rebelo I, Castro EM, et al. Band 3 as a marker of erythrocyte changes in pregnancy. Eur J Haematol 2002 Sep; 69 (3): 145–51

    Google Scholar 

  31. Coimbra S, Castro E, Rocha-Pereira P, et al. The effect of green tea in oxidative stress. Clin Nutr 2006 Oct; 25 (5): 790–6

  32. Catarino C, Rebelo I, Belo L, et al. Erythrocyte changes in preeclampsia: relationship between maternal and cord blood erythrocyte damage. J Perinat Med 2009; 37 (1): 19–27

    Article  PubMed  CAS  Google Scholar 

  33. Rocha S, Vitorino RM, Lemos-Amado FM, et al. Presence of cytosolic peroxiredoxin 2 in the erythrocyte membrane of patients with hereditary spherocytosis. Blood Cells Mol Dis 2008 Jul-Aug; 41 (1): 5–9

  34. Costa E, Rocha S, Rocha-Pereira P, et al. Band 3 profile as amarker of erythrocyte changes in chronic kidney disease patients. Open Clin Chem J 2008; 1: 57–63

    Article  CAS  Google Scholar 

  35. Santos-Silva A, Castro EM, Teixeira NA, et al. Altered erythrocyte membrane band 3 profile as a marker in patients at risk for cardiovascular disease. Atherosclerosis 1995 Aug; 116 (2): 199–209

  36. Santos-Silva A, Castro EM, Teixeira NA, et al. Erythrocyte membrane band 3 profile imposed by cellular aging, by activated neutrophils and by neutrophilic elastase. Clin Chim Acta 1998 Jul 28; 275 (2): 185–96

  37. Gornicki A, Gutsze A. Erythrocyte membrane fluidity changes in psoriasis: an EPR study. J Dermatol Sci 2001 Sep; 27 (1): 27–30

  38. Gornicki A. Domain structure of erythrocyte membranes in psoriasis: an EPR study. J Dermatol Sci 2002 Sep; 29 (3): 214–21

  39. Corrocher R, Bassi A, Gandini A, et al. Transmembrane cation fluxes and fatty acid composition of erythrocytes in psoriatic patients. Clin Chim Acta 1990 Jan 31; 186 (3): 335–44

  40. Schopf RE, Langendorf Y, Benz RE, et al. A highly decreased binding of cyclic adenosine monophosphate to protein kinase A in erythrocyte membranes is specific for active psoriasis. J Invest Dermatol 2002 Jul; 119 (1): 160–5

    Google Scholar 

  41. Shimizu T, Takakuwa Y, Koizumi H, et al. Localization of immuno-analogues of erythrocyte protein 4.1 and spectrin in epidermis of psoriasis vulgaris. Histochem Cell Biol 1995 May; 103 (5): 363–8

    Google Scholar 

  42. Lebwohl M, Feldman SR, Walther R, et al. Clinical management of psoriasis: principles and practice. Cutis 2001 Jan; 67 (1 Suppl.): 1–15

    Google Scholar 

  43. Frederiksson T, Pettersson U. Severe psoriasis: oral therapy with a new retinoid. Dermatologica 1978; 157: 238–44

    Article  Google Scholar 

  44. Dodge JT, Mitchell C, Hanahan DJ. The preparation and chemical characteristics of hemoglobin-free ghosts of human erythrocytes. Arch Biochem Biophys 1963 Jan; 100: 119–30

    Google Scholar 

  45. Bradford MM. Arapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976 May 7; 72: 248–54

  46. Niehaus Jr WG, Samuelsson B. Formation of malonaldehyde from phospholipid arachidonate during microsomal lipid peroxidation. Eur J Biochem 1968 Oct 17; 6 (1): 126–30

  47. Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 1970 Aug 15; 227 (5259): 680–5

  48. Towbin H, Staehelin T, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A 1979 Sep; 76 (9): 4350–4

    Google Scholar 

  49. Czerwinski M, Wasniowska K, Steuden I, et al. Degradation of the human erythrocyte membrane band 3 studied with monoclonal antibody directed against an epitope on the cytoplasmic fragment of band 3. Eur J Biochem 1988 Jul 1; 174 (4): 647–54

  50. Mamus SW, Beck-Schroeder S, Zanjani ED. Suppression of normal human erythropoiesis by gamma interferon in vitro: role of monocytes and T lymphocytes. J Clin Invest 1985 May; 75 (5): 1496–503

    Google Scholar 

  51. Means Jr RT, Krantz SB. Inhibition of human erythroid colony-forming units by tumor necrosis factor requires beta interferon. J Clin Invest 1993 Feb; 91 (2): 416–9

  52. Lebwohl M, Ali S. Treatment of psoriasis: part 1. Topical therapy and phototherapy. J Am Acad Dermatol 2001 Oct; 45 (4): 487–98; quiz 499-502

  53. Lebwohl M, Ting PT, Koo JY. Psoriasis treatment: traditional therapy. Ann Rheum Dis 2005 Mar; 64 Suppl. 2: ii83–6

    Google Scholar 

  54. Silny W, Pehamberger H, Zielinsky C, et al. Effect of PUVA treatment on the locomotion of polymorphonuclear leukocytes and mononuclear cells in psoriasis. J Invest Dermatol 1980 Aug; 75 (2): 187–8

    Google Scholar 

  55. Kapuscinska R, Wysocka J, Niczyporuk W, et al. Cytofluorimetric assay for evaluation of CD16 receptor expression and myeloperoxidase (MPO) activity of neutrophils in patients with psoriasis vulgaris treated with PUVA. Wiad Lek 2004; 57 (11-12): 599–602

    PubMed  Google Scholar 

  56. Bredberg A, Forsgren A. Effects of in vitro PUVA on human leukocyte function. Br J Dermatol 1984 Aug; 111 (2): 159–68

    Google Scholar 

  57. Piskin G, Tursen U, Bos JD, et al. IL-4 expression by neutrophils in psoriasis lesional skin upon high-dose UVB exposure. Dermatology 2003; 207 (1): 51–3

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This study was supported by FCT (POCI/SAU — OBS/58600/2004) and by Fundação para a Ciência e Tecnologia (FCT: POCI/SAU — OBS/58600/2004) and Fundo Europeu de Desenvolvimento Regional (FEDER). The authors have no conflicts of interest that are directly relevant to the content of this study.

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Authors and Affiliations

  1. Department of Biological Sciences, Biochemistry, Faculty of Pharmacy, University of Porto, R Aníbal Cunha 164, 4050-047, Porto, Portugal

    Susana Coimbra, Luís Belo, Susana Rocha, Elisabeth Castro & Alice Santos-Silva

  2. Institute of Cellular and Molecular Biology (IBMC), University of Porto, Porto, Portugal

    Susana Coimbra, Luís Belo, Susana Rocha, Alexandre Quintanilha, Elisabeth Castro, Petronila Rocha-Pereira & Alice Santos-Silva

  3. Center of Investigation of Technologies of Health (CITS) — IPSN-CESPU, Gandra-Paredes, Portugal

    Susana Coimbra

  4. Dermatology Service, University Hospitals of Coimbra, Coimbra, Portugal

    Hugo Oliveira & Américo Figueiredo

  5. Institute of Experimental Pharmacology and Therapeutics, IBILI, Faculty of Medicine, University of Coimbra, Coimbra, Portugal

    Flávio Reis & Frederico Teixeira

  6. Institute for Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal

    Alexandre Quintanilha

  7. Center of Investigation of Health Sciences (CICS), University of Beira Interior, Covilhã, Portugal

    Petronila Rocha-Pereira

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  1. Susana Coimbra
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Correspondence to Susana Coimbra.

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Coimbra, S., Oliveira, H., Reis, F. et al. Erythroid Disturbances Before and After Treatment of Portuguese Psoriasis Vulgaris Patients. Am J Clin Dermatol 13, 37–47 (2012). https://doi.org/10.2165/11592110-000000000-00000

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