Alpha-1 antitrypsin, retinol binding protein and keratin 10 alterations in patients with psoriasis vulgaris, a proteomic approach

Document Type: Original Article


1 Cellular and Molecular Biology Research Center, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran

2 Department of Biochemistry, Faculty of Science, University of Sistan & Baluchestan, Zahedan, Iran

3 Department of Biochemistry, School of Veterinary Medicine, Shiraz University, Shiraz, Iran

4 Department of Clinical Biochemistry, Zahedan University of Medical Sciences, Zahedan, Iran

5 Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran


Objective(s):Psoriasis is an autoimmune disease that appears on the skin. Although psoriasis is clinically and histologically well characterized, its pathogenesis is unknown in detail. The aims of this study were to evaluate the proteome of psoriatic patients' sera and to compare them with those of normal healthy human to find valuable biomarkers.
Materials and Methods: In a case-control study, twenty cases of white patients with psoriasis vulgaris, 10 males and 10 females and sixteen healthy controls, 8 males and 8 females were enrolled in the study. The serum protein expression patterns obtained after depletion of albumin were compared by using two dimensional gel electrophoresis (2-DE) coupled to MALDI/TOF-TOF to identify disease associated proteins.
Results: Differential expression of nine protein spots representing four unique proteins including alpha-1 antitrypsin, retinol binding protein, keratin 10 and an unknown protein (with pI 6.47 and molecular weight of 19941 Da), between psoriatic and healthy human serum were found. Furthermore, expression of four new alpha-1 antitrypsin isoforms with different molecular weight and isoelectric point were observed in psoriatic serums in this research for the first time.
Conclusion: A unique proteomic profiling with abnormal expression of alpha-1 antitrypsin and presence of keratin 10 in sera of psoriasis patients were observed that may constitute new and useful findings of psoriasis and offer a clue to a better understanding of the inflammatory pathway.


1. Raychaudhuri SP, Farber EM. The prevalence of psoriasis in the world. J Eur Acad Dermatol Venereol 2001; 15:16-17.

2. Sticherling M. Mechanisms of psoriasis. Drug Discov Today Dis Mech 2005; 2:275-281.

3. Carlen LM, Sanchez F, Bergman AC, Becker S, Hirschberg D, Franzen B et al. Proteome analysis of skin distinguishes acute guttate from chronic plaque psoriasis. J Invest Dermatol 2004; 124:63-69.

4. Nomura I, Gao B, Boguniewicz M, Darst MA, Travers JB, Leung DY. Distinct patterns of gene expression in the skin lesions of atopic dermatitis and psoriasis: a gene microarray analysis. J Allergy Clin Immunol 2003; 112:1195-1202.

5. Oestreicher J, Walters I, Kikuchi T, Gilleaudeau P, Surette J, Schwertschlag U, et al. Molecular classification of psoriasis disease-associated genes through pharmacogenomic expression profiling. Pharmacogenomics J 2001; 1:272-287.

6. Zhou X, Krueger JG, Kao MCJ, Lee E, Du F, Menter A, et al. Novel mechanisms of T-cell and dendritic cell activation revealed by profiling of psoriasis on the 63,100-element oligonucleotide array. Physiol Genomics 2003; 13:69-78.

7. Broome AM, Ryan D, Eckert RL. S100 protein subcellular localization during epidermal differentiation and psoriasis. J Histochem Cytochem 2003; 51:675-685.

8. Al-Mutairi N, EL Eassa B, Nair V. Measurement of vitamin D and cathelicidin (LL-37) levels in patients of psoriasis with co-morbidities. Indian J Dermatol Venereol Leprol 2013; 79:492-496.

9. Ding Y, Yi X, Yu N. Serum IgE levels are increased in patients with generalized pustular psoriasis. Clin Exp Dermatol 2013; 38:549-552.

10. Pivarcsi A, Meisgen F, Xu N, Stahle M, Sonkoly E. Changes in the level of serum microRNAs in psoriasis patients after anti‐tumor necrosis factor‐α therapy. Br J Dermatol 2013; 169:563-570.

11. Nakajima H, Nakajima K, Tarutani M, Sano S. Clear association between serum levels of adipokines and T‐helper 17‐related cytokines in patients with psoriasis. Clin Exp Dermatol 2013; 38:66-70.

12. Kaur S, Zilmer K, Leping V, Zilmer M. Serum methylglyoxal level and its association with oxidative stress and disease severity in patients with psoriasis. Arch Dermatol Res 2013; 305:489-494.

13. Williamson JC, Scheipers P, Schwämmle V, Zibert JR, Beck HC, Jensen ON. A proteomics approach to the identification of biomarkers for psoriasis utilising keratome biopsy. J Proteomics 2013; 94:176-185.

14. Cowen EW, Liu CW, Steinberg SM, Kang S, Vonderheid EC, Kwak HS, et al. Differentiation of tumor-stage mycosis fungoides, psoriasis vulgaris and normal controls in a pilot study using serum proteomic analysis. Br J Dermatol 2007; 157:946-953.

15. Kalenka A, Feldmann RE, Otero K, Maurer MH, Waschke KF, Fiedler F. Changes in the serum proteome of patients with sepsis and septic shock. Anesth Analg 2006; 103:1522-1526.

16. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976; 72:248-254.

17. Jiang L, He L, Fountoulakis M. Comparison of protein precipitation methods for sample preparation prior to proteomic analysis. J Chrom A 2004; 1023:317-320.

18. Ahmed N, Barker G, Oliva K, Garfin D, Talmadge K, Georgiou H, et al. An approach to remove albumin for the proteomic analysis of low abundance biomarkers in human serum. Proteomics 2003; 3:1980-1987.

19. Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 1970; 227:680-685.

20. Kazemipour N, Condemine G, Hugouvieux‐Cotte‐Pattat N. The secretome of the plant pathogenic bacterium Erwinia chrysanthemi. Proteomics 2004; 4:3177-3186.

21. Harvima IT, Haapanen L, Ackermann L, Naukkarinen A, Harvima RJ, Horsmanheimo M. Decreased chymase activity is associated with increased levels of protease inhibitors in mast cells of psoriatic lesions. Acta Dermatoven-Stockholm 1999; 79:98-104.

22. Heng M, Moy R, Lieberman J. Alpha 1‐Antitrypsin deficiency in severe psoriasis. Br J Dermatol 1985; 112:129-133.

23. Nini G, Bianchi L, Angelini E, Corleto V, Gatti S, Carrozzo A. Evaluation of serine alpha 1-antitrypsin and polymorphonuclear leukocyte elastase contents and their immunogenetic correlation in psoriasis. Acta Dermatoven Supp 1994; 186:143-145.

24. Scott L, Evans E, Dawes P, Russell G, Mattey D. Comparison of IgA-alpha1-antitrypsin levels in rheumatoid arthritis and seronegative oligoarthritis: complex formation is not associated with inflammation per se. Br J Rheumatol 1998; 37:398-404.

25. Pavez Lorie E, Cools M, Borgers M, Wouters L, Shroot B, Hagforsen E, et al. Topical treatment with CYP26 inhibitor talarozole (R115866) dose dependently alters the expression of retinoid‐regulated genes in normal human epidermis. Br J Dermatol 2009; 160:26-36.

26. Taylor GA, Shalita AR. Retinoid therapy of acne and sebocyte-related disorders. Basic Clin Dermatol 2007; 39:103-123.

27. Rabilloud T, Asselineau D, Bailly C, Miquel C, Tarroux P, Darmon M. Study of the human epidermal differentiation by two dimensional electrophoresis. In: Schaefer-Nielsen C, editor. Electrophoresis, 88th ed. Munich: Verlag Chemie; 1989.

28. Roos TC, Jugert FK, Merk HF, Bickers DR. Retinoid metabolism in the skin. Pharmacol Rev 1998; 50:315-333.

29. Schweizer J, Bowden PE, Coulombe PA, Langbein L, Lane EB, Magin TM, et al. New consensus nomenclature for mammalian keratins. J Cell Biol 2006; 174:169-174.

30. Muller FB, Huber M, Kinaciyan T, Hausser I, Schaffrath C, Krieg T, et al. A human keratin 10 knockout causes recessive epidermolytic hyperkeratosis. Hum Mol Gen 2006; 15:1133-1141.

31. Paramio JM, Segrelles C, Ruiz S, Jorcano JL. Inhibition of protein kinase B (PKB) and PKCζ mediates keratin K10-induced cell cycle arrest. Mol Cell Biol 2001; 21:7449-7459.

32. Mommers J, Van Rossum M, Van Erp P, Van De Kerkhof P. Changes in keratin 6 and keratin 10 (co-) expression in lesional and symptomless skin of spreading psoriasis. Dermatol 2000; 201:15-20.