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HLA-Cw6 and the Genetic Predisposition to Psoriasis: a Meta-Analysis of Published Serologic Studies

1999; Elsevier BV; Volume: 113; Issue: 4 Linguagem: Inglês

10.1046/j.1523-1747.1999.00724.x

1523-1747

Eleanor Mallon, Clareann H. Bunker, Roger Newson,

T-cell and B-cell Immunology

To the Editor: Postulated genetic factors in psoriasis include human leukocyte antigen associations. HLA-Cw6 is the most frequently described association and has been confirmed in many racial groups. The frequency of many HLA-C alleles, however, is underestimated by serology and some antigens such as HLA-Cw6 are thought to be consistently assigned incorrectly by serology (Bunce et al., 1996Bunce M. Barnardo M. Procter J. Marsh S.G.E. Vilches C. Welsh K.I. High resolution HLA-C typing by PCR-SSP. identification of allelic frequencies and linkage disequilibria in 604 unrelated random UK Caucasians and a comparison with serology.Tissue Antigens. 1996; 48: 680-691Crossref PubMed Scopus (91) Google Scholar). The low surface expression of HLA-C molecules together with the lack of typing reagents account for the fact that 20%–50% of populations studied so far carry undefined HLA-C alleles, collectively called Cw "blank" (Levine and Yang, 1994Levine J.E. Yang S.Y. SSOP typing of the Tenth International Histocompatibility Workshop reference cell lines for HLA-C alleles.Tissue Antigens. 1994; 44: 174-183Crossref PubMed Scopus (57) Google Scholar). Using a high resolution polymerase chain reaction with sequence-specific primers we have recently reported the strong association of HLA-Cw*0602 in a U.K. Caucasian population with chronic plaque psoriasis (Mallon et al., 1997Mallon E. Bunce M. Welsh K. Wojnarowska F. HLA-Cw*0602 is a susceptibility factor in type I psoriasis, and evidence Ala-73 is increased in male type 1 psoriatics.J Invest Dermatol. 1997; 109: 183-186Crossref PubMed Scopus (81) Google Scholar), HIV-associated psoriasis (Mallon et al., 1998Mallon E. Young D. Bunce M. Gotch F.M. Easterbrook P.J. Newson R. Bunker C.B. HLA-Cw*0602 and HIV-associated psoriasis.Br J Dermatol. 1998; 139: 527-533Crossref PubMed Scopus (40) Google Scholar), and streptococcal associated guttate psoriasis. 1Mallon E, Bunce M, Savoie H, Gotch F, Bunker CB: HLA-Cw*0602 and guttate psoriasis. J Invest Dermatol 110:618 1998 (abstr.) Case-control HLA association studies are limited by the fact that control populations may be derived from a different gene pool. Recent evidence from genetic linkage studies supports a role for the HLA-C locus in the pathogenesis of chronic plaque psoriasis; linkage to the major histocompatibility complex region on chromosome 6p21 (including to the HLA-C locus) has been demonstrated indicating that one or more genes located within the major histocompatibility complex and close to class I HLA loci may represent the major determinant of the genetic basis of psoriasis (Trembath et al., 1997Trembath R.C. Clough R.L. Rosbotham J. et al.Identification of a major susceptibility locus on chromosome 6p and evidence for further disease loci revealed by a two stage genome-wide search in psoriasis.Hum Mol Genet. 1997; 6: 813-820Crossref PubMed Scopus (440) Google Scholar). We thought it worthwhile to examine all available published data on the association of HLA-Cw6 with psoriasis. We have examined data from serologic studies investigating HLA-C antigens in psoriasis and included all studies that provided usable data up to December 1998. The results emphasize the importance of HLA-C, or a gene in linkage disequilibrium with HLA-C, in the predisposition to psoriasis, particularly in guttate psoriasis and psoriasis of early onset. Medline, PubMed, and EMBASE database searches were performed to obtain all published serologic studies available from 1966 to December 1998: MeSH (medical subjects heading) terms used were "immunogenetics and psoriasis""HLA and psoriasis" and "HLA-C and psoriasis". References were also sought from published research by using the Science Citation Index and by searching references in published studies and abstracts. The search was not restricted to the English language. Inclusion criteria for studies incorporated in the meta-analysis were that: (i) HLA-Cw6 was included in the investigation of HLA associations in patients with psoriasis; (ii) a control population without psoriasis was also studied; and (iii) a study did not use the same data as previous studies. The search uncovered 14 studies (Brenner et al., 1978Brenner W. Gschnail F. Mayr W.R. HLA B13, B17, B36 and Cw6 in psoriasis vulgaris.Arch Dermatol Res. 1978; 262: 337-339Crossref PubMed Scopus (74) Google Scholar;Murray et al., 1980Murray C. Mann D. Gerber L. Barth W. Perlmann S. Decker J. Nigra T. Histocompatibility alloantigens in psoriasis and psoriatic arthritis.J Clin Invest. 1980; 66: 670-675Crossref PubMed Scopus (85) Google Scholar;Tiilikainen et al., 1980Tiilikainen A. Lassus A. Karvonen J. Vartiainen P. Julin M. Psoriasis Hla-Cw6.Br J Dermatol. 1980; 102: 179-184Crossref PubMed Scopus (254) Google Scholar;Laurentaci et al., 1982Laurentaci G. Lomuto M. Favoino B. Immunogenetic analysis of association between HLA antigens and psoriasis vulgaris: population and family studies.Dermatologica. 1982; 165: 591-600Crossref PubMed Scopus (7) Google Scholar;Armstrong et al., 1983Armstrong R.D. Panayi G.S. Welsh K.I. Histocompatibility antigens in psoriasis, psoriatic arthropathy and ankylosing spondylitis.Ann Rheum Dis. 1983; 42: 142-146Crossref PubMed Scopus (64) Google Scholar;Economidou et al., 1985Economidou J. Papasteriades C. Varla-Leftherioti M. Vareltzidis A. Stratigos J. Human lymphocyte antigens A, B and C in Greek patients with psoriasis: relation to age and clinical expression of the disease.J Am Acad Dermatol. 1985; 13: 578-582Abstract Full Text PDF PubMed Scopus (19) Google Scholar;Ozawa et al., 1988Ozawa A. Ohkido M. Inoko H. Ando A. Tsuji K. Specific restriction fragment length polymorphism on the HLA-C region and susceptibility to psoriasis vulgaris.J Invest Dermatol. 1988; 90: 402-405Abstract Full Text PDF PubMed Google Scholar;Nakagawa et al., 1991Nakagawa H. Akazaki S. Asahina A. et al.Study of HLA class I, class II and complement genes (C2, C4A, C4B and BF) in Japanese psoriatics and analysis of a newly-found high-risk haplotype by pulsed field gel electrophoresis.Arch Dermatol Res. 1991; 283: 281-284Crossref PubMed Scopus (58) Google Scholar;Chablani et al., 1992Chablani U.A. Contractor N.M. Gadgil R.B. HLA and complement C4 studies in psoriasis vulgaris.Natl Med J India. 1992; 5: 8-11PubMed Google Scholar;Cao et al., 1993Cao K. Song F. Li H. Xu S. Liu Z. Su X. Wang F. Association between HLA antigens and families with psoriasis vulgaris.Chinese Med J. 1993; 106: 132-135PubMed Google Scholar;Ikäheimo et al., 1994Ikäheimo I. Silvennoinen-Kassinen S. Karvonen J. Tiilikainen A. Alanine at position 73 of HLA-C is associated with psoriasis vulgaris in Finland.Br J Dermatol. 1994; 131: 257-259Crossref PubMed Scopus (33) Google Scholar;Roitberg-Tambur et al., 1994Roitberg-Tambur A. Friedmann A. Tzfoni E. et al.Do specific pockets of HLA-C molecules predispose Jewish patients to psoriasis vulgaris?.J Am Acad Dermatol. 1994; 31: 964-968Abstract Full Text PDF PubMed Scopus (44) Google Scholar;Gonzaga et al., 1996Gonzaga H.F.S. Torres E. Alchorne M. Gerbase-Delima M. Both psoriasis and benign migratory glossitis are associated with HLA-Cw6.Br J Dermatol. 1996; 135: 368-370Crossref PubMed Scopus (54) Google Scholar;Schmitt-Egenolf et al., 1996Schmitt-Egenolf M. Eiermann T.H. Boehncke W.-H. Ständer M. Sterry W. Familial juvenile onset psoriasis is associated with human leucocyte antigen (HLA) class I side of the extended haplotype Cw6–B57-DRB1*0701-DQA1*0201-DQB1*0303: a population and family based study.J Invest Dermatol. 1996; 106: 711-714Abstract Full Text PDF PubMed Scopus (112) Google Scholar) that met these inclusion criteria. Relevant data (HLA-C phenotype frequencies in cases and controls) were extracted from the published papers obtained (Table 1). Odds ratios, confidence limits, and significance values for HLA-Cw6 were calculated (Table 2) usingEpi Info, 1996Epi Info Version 6: A word processing, database and statistics system for epidemiology on microcomputers. US Department of Health and Human Services. Epi Info @ http://www.cdc.gov/epo/epi/epiinfo.htm, 1996Google Scholar. Meta-analysis was performed on the results of HLA-Cw6 typing by logistic regression using the Stata Statistical Package (Stata Statistical Software, 1997Stata Statistical Software, Release 5.0. Texas: College Station, Stata Corporation, 1997Google Scholar). Baseline odds for psoriasis in Cw6 negative patients was estimated for each individual study and a common odds ratio, interpreted as the relative risk, was estimated over all studies. Robust variance formulae were used to calculate confidence limits, allowing for the possibility that true relative risks might vary slightly from one study to another, so that the common relative risk would be an appropriately weighted average. Meta-analysis was performed on studies in each of five psoriasis subgroups: group 1, early-onset psoriasis; group 2, late-onset psoriasis; group 3, guttate psoriasis (one study only); group 4, psoriasis of unspecified type; group 5, psoriasis vulgaris. Three studies (Brenner et al., 1978Brenner W. Gschnail F. Mayr W.R. HLA B13, B17, B36 and Cw6 in psoriasis vulgaris.Arch Dermatol Res. 1978; 262: 337-339Crossref PubMed Scopus (74) Google Scholar;Tiilikainen et al., 1980Tiilikainen A. Lassus A. Karvonen J. Vartiainen P. Julin M. Psoriasis Hla-Cw6.Br J Dermatol. 1980; 102: 179-184Crossref PubMed Scopus (254) Google Scholar;Schmitt-Egenolf et al., 1996Schmitt-Egenolf M. Eiermann T.H. Boehncke W.-H. Ständer M. Sterry W. Familial juvenile onset psoriasis is associated with human leucocyte antigen (HLA) class I side of the extended haplotype Cw6–B57-DRB1*0701-DQA1*0201-DQB1*0303: a population and family based study.J Invest Dermatol. 1996; 106: 711-714Abstract Full Text PDF PubMed Scopus (112) Google Scholar) were included in the meta-analysis of more than one group.Table 1HLA-Cw6 typing results in serologic studies used in meta-analysisPsoriasis typeStudy (country)Cases Cw6 +veControls Cw6 +veCases Cw6 –veControls Cw6 –veI aAge of onset between 10 and 20 y.Brenner et al., 1978Brenner W. Gschnail F. Mayr W.R. HLA B13, B17, B36 and Cw6 in psoriasis vulgaris.Arch Dermatol Res. 1978; 262: 337-339Crossref PubMed Scopus (74) Google Scholar (Austria)4832993I bAge of onset < 30 y.Schmitt-Egenolf et al., 1996Schmitt-Egenolf M. Eiermann T.H. Boehncke W.-H. Ständer M. Sterry W. Familial juvenile onset psoriasis is associated with human leucocyte antigen (HLA) class I side of the extended haplotype Cw6–B57-DRB1*0701-DQA1*0201-DQB1*0303: a population and family based study.J Invest Dermatol. 1996; 106: 711-714Abstract Full Text PDF PubMed Scopus (112) Google Scholar (Germany)493111115II cAge of onset between 35 and 45 y.Brenner et al., 1978Brenner W. Gschnail F. Mayr W.R. HLA B13, B17, B36 and Cw6 in psoriasis vulgaris.Arch Dermatol Res. 1978; 262: 337-339Crossref PubMed Scopus (74) Google Scholar (Austria)9321193II dAge of onset > 40 y.Schmitt-Egenolf et al., 1996Schmitt-Egenolf M. Eiermann T.H. Boehncke W.-H. Ständer M. Sterry W. Familial juvenile onset psoriasis is associated with human leucocyte antigen (HLA) class I side of the extended haplotype Cw6–B57-DRB1*0701-DQA1*0201-DQB1*0303: a population and family based study.J Invest Dermatol. 1996; 106: 711-714Abstract Full Text PDF PubMed Scopus (112) Google Scholar (Germany)133117115GuttateTiilikainen et al., 1980Tiilikainen A. Lassus A. Karvonen J. Vartiainen P. Julin M. Psoriasis Hla-Cw6.Br J Dermatol. 1980; 102: 179-184Crossref PubMed Scopus (254) Google Scholar (Finland)16346428UnspecifiedBrenner et al., 1978Brenner W. Gschnail F. Mayr W.R. HLA B13, B17, B36 and Cw6 in psoriasis vulgaris.Arch Dermatol Res. 1978; 262: 337-339Crossref PubMed Scopus (74) Google Scholar (Austria)57322093UnspecifiedMurray et al., 1980Murray C. Mann D. Gerber L. Barth W. Perlmann S. Decker J. Nigra T. Histocompatibility alloantigens in psoriasis and psoriatic arthritis.J Clin Invest. 1980; 66: 670-675Crossref PubMed Scopus (85) Google Scholar (USA)301730109UnspecifiedArmstrong et al., 1983Armstrong R.D. Panayi G.S. Welsh K.I. Histocompatibility antigens in psoriasis, psoriatic arthropathy and ankylosing spondylitis.Ann Rheum Dis. 1983; 42: 142-146Crossref PubMed Scopus (64) Google Scholar (England)423212121UnspecifiedEconomidou et al., 1985Economidou J. Papasteriades C. Varla-Leftherioti M. Vareltzidis A. Stratigos J. Human lymphocyte antigens A, B and C in Greek patients with psoriasis: relation to age and clinical expression of the disease.J Am Acad Dermatol. 1985; 13: 578-582Abstract Full Text PDF PubMed Scopus (19) Google Scholar (Greece)333058172UnspecifiedOzawa et al., 1988Ozawa A. Ohkido M. Inoko H. Ando A. Tsuji K. Specific restriction fragment length polymorphism on the HLA-C region and susceptibility to psoriasis vulgaris.J Invest Dermatol. 1988; 90: 402-405Abstract Full Text PDF PubMed Google Scholar (Japan)271377937Psoriasis vulgarisTiilikainen et al., 1980Tiilikainen A. Lassus A. Karvonen J. Vartiainen P. Julin M. Psoriasis Hla-Cw6.Br J Dermatol. 1980; 102: 179-184Crossref PubMed Scopus (254) Google Scholar (Finland)173420428Psoriasis vulgarisLaurentaci et al., 1982Laurentaci G. Lomuto M. Favoino B. Immunogenetic analysis of association between HLA antigens and psoriasis vulgaris: population and family studies.Dermatologica. 1982; 165: 591-600Crossref PubMed Scopus (7) Google Scholar (Italy)542468152Psoriasis vulgarisNakagawa et al., 1991Nakagawa H. Akazaki S. Asahina A. et al.Study of HLA class I, class II and complement genes (C2, C4A, C4B and BF) in Japanese psoriatics and analysis of a newly-found high-risk haplotype by pulsed field gel electrophoresis.Arch Dermatol Res. 1991; 283: 281-284Crossref PubMed Scopus (58) Google Scholar (Japan)7072100Psoriasis vulgarisChablani et al., 1992Chablani U.A. Contractor N.M. Gadgil R.B. HLA and complement C4 studies in psoriasis vulgaris.Natl Med J India. 1992; 5: 8-11PubMed Google Scholar (India)36373195Psoriasis vulgarisCao et al., 1993Cao K. Song F. Li H. Xu S. Liu Z. Su X. Wang F. Association between HLA antigens and families with psoriasis vulgaris.Chinese Med J. 1993; 106: 132-135PubMed Google Scholar (China)211099Psoriasis vulgarisIkäheimo et al., 1994Ikäheimo I. Silvennoinen-Kassinen S. Karvonen J. Tiilikainen A. Alanine at position 73 of HLA-C is associated with psoriasis vulgaris in Finland.Br J Dermatol. 1994; 131: 257-259Crossref PubMed Scopus (33) Google Scholar (Finland)351030178Psoriasis vulgarisRoitberg-Tambur et al., 1994Roitberg-Tambur A. Friedmann A. Tzfoni E. et al.Do specific pockets of HLA-C molecules predispose Jewish patients to psoriasis vulgaris?.J Am Acad Dermatol. 1994; 31: 964-968Abstract Full Text PDF PubMed Scopus (44) Google Scholar (Israel)74621212Psoriasis vulgarisGonzaga et al., 1996Gonzaga H.F.S. Torres E. Alchorne M. Gerbase-Delima M. Both psoriasis and benign migratory glossitis are associated with HLA-Cw6.Br J Dermatol. 1996; 135: 368-370Crossref PubMed Scopus (54) Google Scholar (Brazil)13209139Psoriasis vulgarisSchmitt-Egenolf et al., 1996Schmitt-Egenolf M. Eiermann T.H. Boehncke W.-H. Ständer M. Sterry W. Familial juvenile onset psoriasis is associated with human leucocyte antigen (HLA) class I side of the extended haplotype Cw6–B57-DRB1*0701-DQA1*0201-DQB1*0303: a population and family based study.J Invest Dermatol. 1996; 106: 711-714Abstract Full Text PDF PubMed Scopus (112) Google Scholar (Germany)623128115a Age of onset between 10 and 20 y.b Age of onset < 30 y.c Age of onset between 35 and 45 y.d Age of onset > 40 y. Open table in a new tab Table 2Odds ratio for HLA-Cw6 and psoriasis from serologic studiesPsoriasis typeStudynOdds ratio95% CL aConfidence limits.p-value bFisher's exact (two-tailed) p value is given.I cPsoriasis vulgaris "including eruptive type, plaque type and seborrhoeic type" age of onset between 10 and 20 y.Brenner et al., 1978Brenner W. Gschnail F. Mayr W.R. HLA B13, B17, B36 and Cw6 in psoriasis vulgaris.Arch Dermatol Res. 1978; 262: 337-339Crossref PubMed Scopus (74) Google Scholar5715.506.50, 39.390.000000I d"Chronic stable psoriasis" age of onset < 30 y.Schmitt-Egenolf et al., 1996Schmitt-Egenolf M. Eiermann T.H. Boehncke W.-H. Ständer M. Sterry W. Familial juvenile onset psoriasis is associated with human leucocyte antigen (HLA) class I side of the extended haplotype Cw6–B57-DRB1*0701-DQA1*0201-DQB1*0303: a population and family based study.J Invest Dermatol. 1996; 106: 711-714Abstract Full Text PDF PubMed Scopus (112) Google Scholar6016.627.30, 38.940.000000II ePsoriasis vulgaris "including eruptive type, plaque type and seborrhoeic type" age of onset between 35 and 45 y.Brenner et al., 1978Brenner W. Gschnail F. Mayr W.R. HLA B13, B17, B36 and Cw6 in psoriasis vulgaris.Arch Dermatol Res. 1978; 262: 337-339Crossref PubMed Scopus (74) Google Scholar202.380.79, 6.940.106200II f"Chronic stable psoriasis" Age of onset > 40 y.Schmitt-Egenolf et al., 1996Schmitt-Egenolf M. Eiermann T.H. Boehncke W.-H. Ständer M. Sterry W. Familial juvenile onset psoriasis is associated with human leucocyte antigen (HLA) class I side of the extended haplotype Cw6–B57-DRB1*0701-DQA1*0201-DQB1*0303: a population and family based study.J Invest Dermatol. 1996; 106: 711-714Abstract Full Text PDF PubMed Scopus (112) Google Scholar302.841.13, 6.950.018900GuttateTiilikainen et al., 1980Tiilikainen A. Lassus A. Karvonen J. Vartiainen P. Julin M. Psoriasis Hla-Cw6.Br J Dermatol. 1980; 102: 179-184Crossref PubMed Scopus (254) Google Scholar2233.5711.37, 109.830.000000UnspecifiedBrenner et al., 1978Brenner W. Gschnail F. Mayr W.R. HLA B13, B17, B36 and Cw6 in psoriasis vulgaris.Arch Dermatol Res. 1978; 262: 337-339Crossref PubMed Scopus (74) Google Scholar778.284.14, 16.750.000000UnspecifiedMurray et al., 1980Murray C. Mann D. Gerber L. Barth W. Perlmann S. Decker J. Nigra T. Histocompatibility alloantigens in psoriasis and psoriatic arthritis.J Clin Invest. 1980; 66: 670-675Crossref PubMed Scopus (85) Google Scholar606.412.95, 14.070.000000UnspecifiedArmstrong et al., 1983Armstrong R.D. Panayi G.S. Welsh K.I. Histocompatibility antigens in psoriasis, psoriatic arthropathy and ankylosing spondylitis.Ann Rheum Dis. 1983; 42: 142-146Crossref PubMed Scopus (64) Google Scholar5413.235.93, 30.540.000000UnspecifiedEconomidou et al., 1985Economidou J. Papasteriades C. Varla-Leftherioti M. Vareltzidis A. Stratigos J. Human lymphocyte antigens A, B and C in Greek patients with psoriasis: relation to age and clinical expression of the disease.J Am Acad Dermatol. 1985; 13: 578-582Abstract Full Text PDF PubMed Scopus (19) Google Scholar913.261.75, 6.050.000094UnspecifiedOzawa et al., 1988Ozawa A. Ohkido M. Inoko H. Ando A. Tsuji K. Specific restriction fragment length polymorphism on the HLA-C region and susceptibility to psoriasis vulgaris.J Invest Dermatol. 1988; 90: 402-405Abstract Full Text PDF PubMed Google Scholar10425.2711.95, 55.250.000000Psoriasis vulgarisTiilikainen et al., 1980Tiilikainen A. Lassus A. Karvonen J. Vartiainen P. Julin M. Psoriasis Hla-Cw6.Br J Dermatol. 1980; 102: 179-184Crossref PubMed Scopus (254) Google Scholar3710.704.75, 23.630.000000Psoriasis vulgarisLaurentaci et al., 1982Laurentaci G. Lomuto M. Favoino B. Immunogenetic analysis of association between HLA antigens and psoriasis vulgaris: population and family studies.Dermatologica. 1982; 165: 591-600Crossref PubMed Scopus (7) Google Scholar1225.032.78, 9.200.000000Psoriasis vulgarisNakagawa et al., 1991Nakagawa H. Akazaki S. Asahina A. et al.Study of HLA class I, class II and complement genes (C2, C4A, C4B and BF) in Japanese psoriatics and analysis of a newly-found high-risk haplotype by pulsed field gel electrophoresis.Arch Dermatol Res. 1991; 283: 281-284Crossref PubMed Scopus (58) Google Scholar79∞1.92, ∞0.002794Psoriasis vulgarisChablani et al., 1992Chablani U.A. Contractor N.M. Gadgil R.B. HLA and complement C4 studies in psoriasis vulgaris.Natl Med J India. 1992; 5: 8-11PubMed Google Scholar672.981.54, 5.750.000570Psoriasis vulgarisCao et al., 1993Cao K. Song F. Li H. Xu S. Liu Z. Su X. Wang F. Association between HLA antigens and families with psoriasis vulgaris.Chinese Med J. 1993; 106: 132-135PubMed Google Scholar1219.800.90, 1178.950.029923Psoriasis vulgarisIkäheimo et al., 1994Ikäheimo I. Silvennoinen-Kassinen S. Karvonen J. Tiilikainen A. Alanine at position 73 of HLA-C is associated with psoriasis vulgaris in Finland.Br J Dermatol. 1994; 131: 257-259Crossref PubMed Scopus (33) Google Scholar6520.778.89, 51.310.000000Psoriasis vulgarisRoitberg-Tambur et al., 1994Roitberg-Tambur A. Friedmann A. Tzfoni E. et al.Do specific pockets of HLA-C molecules predispose Jewish patients to psoriasis vulgaris?.J Am Acad Dermatol. 1994; 31: 964-968Abstract Full Text PDF PubMed Scopus (44) Google Scholar281.540.52, 4.030.440371Psoriasis vulgarisGonzaga et al., 1996Gonzaga H.F.S. Torres E. Alchorne M. Gerbase-Delima M. Both psoriasis and benign migratory glossitis are associated with HLA-Cw6.Br J Dermatol. 1996; 135: 368-370Crossref PubMed Scopus (54) Google Scholar2210.043.40, 29.880.000004Psoriasis vulgarisSchmitt-Egenolf et al., 1996Schmitt-Egenolf M. Eiermann T.H. Boehncke W.-H. Ständer M. Sterry W. Familial juvenile onset psoriasis is associated with human leucocyte antigen (HLA) class I side of the extended haplotype Cw6–B57-DRB1*0701-DQA1*0201-DQB1*0303: a population and family based study.J Invest Dermatol. 1996; 106: 711-714Abstract Full Text PDF PubMed Scopus (112) Google Scholar908.214.34, 15.610.000000a Confidence limits.b Fisher's exact (two-tailed) p value is given.c Psoriasis vulgaris "including eruptive type, plaque type and seborrhoeic type" age of onset between 10 and 20 y.d "Chronic stable psoriasis" age of onset < 30 y.e Psoriasis vulgaris "including eruptive type, plaque type and seborrhoeic type" age of onset between 35 and 45 y.f "Chronic stable psoriasis" Age of onset > 40 y. Open table in a new tab Meta-analysis (Table 3) showed that HLA-Cw6 predicted guttate psoriasis more strongly than type I psoriasis, and type I psoriasis more strongly than type II psoriasis. The other two types of psoriasis (vulgaris and unspecified) are probably mixtures of these three types and show intermediate odds ratios.Table 3Meta-analysis of serologic studiesPsoriasis typeNo of studiesOdds ratiop value95% confidence intervalType I216.040.0009.17, 28.07Type II22.630.0031.40, 4.94Guttate133.570.00012.32, 91.45Unspecified58.480.0006.21, 11.57Psoriasis vulgaris96.460.0004.99, 8.36 Open table in a new tab This meta-analysis is of limited value because publication bias makes it more likely that significant positive associations are published compared with non-significant associations (Easterbrook et al., 1991Easterbrook P.J. Berlin J.A. Gopalan R. Mathews D.R. Publication bias in clinical research.Lancet. 1991; 337: 867-872Abstract PubMed Scopus (2156) Google Scholar) and an accurate meta-analysis should include unpublished data (Bland, 1995Bland M. An Introduction to Medical Statistics. Oxford University Press, Oxford1995Google Scholar). In order to include unpublished data in the meta-analysis of HLA-Cw6 serologic typing results in psoriasis, we invite the contribution of unpublished HLA-C serologic typing results to the authors of this letter.