Logo of annrheumdAnnals of the Rheumatic DiseasesVisit this articleSubmit a manuscriptReceive email alertsContact usBMJ
Ann Rheum Dis. 2000 Dec; 59(12): 975–981.
PMCID: PMC1753043

Anti-ribosomal P protein antibodies detected by immunoblotting in patients with connective tissue diseases: their specificity for SLE and association with IgG anticardiolipin antibodies


OBJECTIVE—To assess the prevalence and clinical and serological associations of anti-ribosomal P protein antibodies (anti-P antibodies) in patients with connective tissue diseases (CTDs) and investigate the immunobiological nature of autoantibody clustering in which anti-P antibodies play a part.
METHODS—IgG anti-P antibodies in the sera of 267 patients with CTDs and 31 healthy subjects were analysed by immunoblotting performed on cytoplasmic extract of Raji cells. 60 patients with systemic lupus erythematosus (SLE), 32 systemic sclerosis, 46 primary Sjögren's syndrome, 16 poly/dermatomyositis, 11 rheumatoid arthritis, 8 undifferentiated CTD, 72 overlap CTD, and 22 primary antiphospholipid syndrome were studied. Anti-P antibodies were affinity purified by elution from nitrocellulose bound antigen and tested by ELISA for their binding activity to cardiolipin.
RESULTS—Anti-P antibodies were detected in 16 (6%) patients and in none of the controls: 12/60 SLE (20%) and 4/80 undifferentiated/overlap patients with CTD (5%). A close association of IgG antibodies with P proteins and with cardiolipin was seen in lupus sera (p=0.0009, odds ratio 18.33). Anti-P antibodies from 9 of 12 anti-P lupus serum samples could be affinity purified and none of the affinity purified fractions cross reacted with ELISA plate coated cardiolipin.
CONCLUSIONS—Anti-P immunoreactivity is a specific marker of SLE and lupus-like disease and its detection is recommended as a powerful diagnostic tool. Anti-P antibodies are strongly clustered with IgG anticardiolipin antibodies in lupus sera, even if they are independently elicited. This suggests that their cognate autoantigens play a part in a common pathogenetic pathway in SLE.

Full Text

The Full Text of this article is available as a PDF (201K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Teh LS, Isenberg DA. Antiribosomal P protein antibodies in systemic lupus erythematosus. A reappraisal. Arthritis Rheum. 1994 Mar;37(3):307–315. [PubMed]
  • Francoeur AM, Peebles CL, Heckman KJ, Lee JC, Tan EM. Identification of ribosomal protein autoantigens. J Immunol. 1985 Oct;135(4):2378–2384. [PubMed]
  • Sato T, Uchiumi T, Arakawa M, Kominami R. Serological association of lupus autoantibodies to a limited functional domain of 28S ribosomal RNA and to the ribosomal proteins bound to the domain. Clin Exp Immunol. 1994 Oct;98(1):35–39. [PMC free article] [PubMed]
  • Elkon KB, Parnassa AP, Foster CL. Lupus autoantibodies target ribosomal P proteins. J Exp Med. 1985 Aug 1;162(2):459–471. [PMC free article] [PubMed]
  • Bonfa E, Parnassa AP, Rhoads DD, Roufa DJ, Wool IG, Elkon KB. Antiribosomal S10 antibodies in humans and MRL/lpr mice with systemic lupus erythematosus. Arthritis Rheum. 1989 Oct;32(10):1252–1261. [PubMed]
  • Sato T, Uchiumi T, Ozawa T, Kikuchi M, Nakano M, Kominami R, Arakawa M. Autoantibodies against ribosomal proteins found with high frequency in patients with systemic lupus erythematosus with active disease. J Rheumatol. 1991 Nov;18(11):1681–1684. [PubMed]
  • Elkon K, Skelly S, Parnassa A, Moller W, Danho W, Weissbach H, Brot N. Identification and chemical synthesis of a ribosomal protein antigenic determinant in systemic lupus erythematosus. Proc Natl Acad Sci U S A. 1986 Oct;83(19):7419–7423. [PMC free article] [PubMed]
  • Iverson GL. Are antibodies to ribosomal P proteins a clinically useful predictor of neuropsychiatric manifestations in patients with systemic lupus erythematosus? Lupus. 1996 Dec;5(6):634–635. [PubMed]
  • Yoshio T, Masuyama JI, Minota S, Kaneko N, Iwamoto M, Okazaki H, Mimori A, Takeda A, Kano S. A close temporal relationship of liver disease to antiribosomal P0 protein antibodies and central nervous system disease in patients with systemic lupus erythematosus. J Rheumatol. 1998 Apr;25(4):681–688. [PubMed]
  • Bonfa E, Elkon KB. Clinical and serologic associations of the antiribosomal P protein antibody. Arthritis Rheum. 1986 Aug;29(8):981–985. [PubMed]
  • Gordon TP, Jovanovich SA, Sykes P, Bradley J, Roberts-Thomson PJ. Detection of autoantibodies to ribosomal P protein using recombinant autoantigen in a quantitative immunoassay. Rheumatol Int. 1990;10(3):99–102. [PubMed]
  • Bonfa E, Golombek SJ, Kaufman LD, Skelly S, Weissbach H, Brot N, Elkon KB. Association between lupus psychosis and anti-ribosomal P protein antibodies. N Engl J Med. 1987 Jul 30;317(5):265–271. [PubMed]
  • van Dam A, Nossent H, de Jong J, Meilof J, ter Borg EJ, Swaak T, Smeenk R. Diagnostic value of antibodies against ribosomal phosphoproteins. A cross sectional and longitudinal study. J Rheumatol. 1991 Jul;18(7):1026–1034. [PubMed]
  • Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, Schaller JG, Talal N, Winchester RJ. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982 Nov;25(11):1271–1277. [PubMed]
  • Vitali C, Bombardieri S, Moutsopoulos HM, Balestrieri G, Bencivelli W, Bernstein RM, Bjerrum KB, Braga S, Coll J, de Vita S, et al. Preliminary criteria for the classification of Sjögren's syndrome. Results of a prospective concerted action supported by the European Community. Arthritis Rheum. 1993 Mar;36(3):340–347. [PubMed]
  • Bohan A, Peter JB. Polymyositis and dermatomyositis (first of two parts). N Engl J Med. 1975 Feb 13;292(7):344–347. [PubMed]
  • Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988 Mar;31(3):315–324. [PubMed]
  • Smolen JS, Steiner G. Mixed connective tissue disease: to be or not to be? Arthritis Rheum. 1998 May;41(5):768–777. [PubMed]
  • Barr SG, Zonana-Nacach A, Magder LS, Petri M. Patterns of disease activity in systemic lupus erythematosus. Arthritis Rheum. 1999 Dec;42(12):2682–2688. [PubMed]
  • Ghirardello A, Doria A, Vesco P, Vaccaro E, Bernardi C, Catani C, Fagiolo U, Gambari PF. Blotting patterns of IgG anti-(U1)RNP antibodies in mixed connective tissue disease. Rheumatol Int. 1996;16(4):145–150. [PubMed]
  • McHugh N, James I, Maddison P. Clinical significance of antibodies to a 68 kDa U1RNP polypeptide in connective tissue disease. J Rheumatol. 1990 Oct;17(10):1320–1328. [PubMed]
  • Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. [PubMed]
  • 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):4350–4354. [PMC free article] [PubMed]
  • Olmsted JB. Affinity purification of antibodies from diazotized paper blots of heterogeneous protein samples. J Biol Chem. 1981 Dec 10;256(23):11955–11957. [PubMed]
  • Zampieri S, Ghirardello A, Doria A, Tonello M, Bendo R, Rossini K, Gambari PF. The use of Tween 20 in immunoblotting assays for the detection of autoantibodies in connective tissue diseases. J Immunol Methods. 2000 May 26;239(1-2):1–11. [PubMed]
  • Bunn CC, Gharavi AE, Hughes GR. Antibodies to extractable nuclear antigens in 173 patients with DNA-binding positive SLE: an association between antibodies to ribonucleoprotein and Sm antigens observed by counterimmunoelectrophoresis. J Clin Lab Immunol. 1982 May;8(1):13–17. [PubMed]
  • Ghirardello A, Doria A, Ruffatti A, Rigoli AM, Vesco P, Calligaro A, Gambari PF. Antiphospholipid antibodies (aPL) in systemic lupus erythematosus. Are they specific tools for the diagnosis of aPL syndrome? Ann Rheum Dis. 1994 Feb;53(2):140–142. [PMC free article] [PubMed]
  • Harris EN. Antiphospholipid antibodies. Br J Haematol. 1990 Jan;74(1):1–9. [PubMed]
  • Thiagarajan P, Pengo V, Shapiro SS. The use of the dilute Russell viper venom time for the diagnosis of lupus anticoagulants. Blood. 1986 Oct;68(4):869–874. [PubMed]
  • de Rooij DJ, van de Putte LB, Habets WJ, Verbeek AL, van Venrooij WJ. The use of immunoblotting to detect antibodies to nuclear and cytoplasmic antigens. Clinical and serological associations in rheumatic diseases. Scand J Rheumatol. 1988;17(5):353–364. [PubMed]
  • Nojima Y, Minota S, Yamada A, Takaku F, Aotsuka S, Yokohari R. Correlation of antibodies to ribosomal P protein with psychosis in patients with systemic lupus erythematosus. Ann Rheum Dis. 1992 Sep;51(9):1053–1055. [PMC free article] [PubMed]
  • Magsaam J, Gharavi AE, Parnassa AP, Weissbach H, Brot N, Elkon KB. Quantification of lupus anti-ribosome P antibodies using a recombinant P2 fusion protein and determination of the predicted amino acid sequence of the autoantigen in patients' mononuclear cells. Clin Exp Immunol. 1989 May;76(2):165–171. [PMC free article] [PubMed]
  • Watanabe T, Sato T, Uchiumi T, Arakawa M. Neuropsychiatric manifestations in patients with systemic lupus erythematosus: diagnostic and predictive value of longitudinal examination of anti-ribosomal P antibody. Lupus. 1996 Jun;5(3):178–183. [PubMed]
  • Caponi L, Pegoraro S, Di Bartolo V, Rovero P, Revoltella R, Bombardieri S. Autoantibodies directed against ribosomal P proteins: use of a multiple antigen peptide as the coating agent in ELISA. J Immunol Methods. 1995 Feb 27;179(2):193–202. [PubMed]
  • Isshi K, Hirohata S. Association of anti-ribosomal P protein antibodies with neuropsychiatric systemic lupus erythematosus. Arthritis Rheum. 1996 Sep;39(9):1483–1490. [PubMed]
  • Yoshio T, Masuyama JI, Minota S, Iwamoto M, Mimori A, Takeda A, Okazaki H, Kano S. Correlation of serum IgG antibodies to recombinant P0 fusion protein with IgG antibodies to carboxyl-terminal 22 synthetic peptides and carboxyl-terminal 22 amino acid-deleted recombinant P0 fusion protein in patients with systemic lupus erythematosus. Arthritis Rheum. 1997 Jul;40(7):1364–1365. [PubMed]
  • Fujimoto M, Sato S, Takehara K, Nojima Y, Soma Y, Kikuchi K, Ihn H, Igarashi A, Tamaki K. Detection of antiribosomal P protein antibodies in patients with systemic sclerosis. Br J Rheumatol. 1995 Oct;34(10):908–911. [PubMed]
  • Hamasaki K, Mimura T, Kanda H, Morino N, Yazaki Y, Nojima Y. Development of systemic lupus erythematosus in a rheumatoid arthritis patient with anti-ribosomal P protein antibody. Lupus. 1997;6(9):734–736. [PubMed]
  • Torre JC, Mozo L, Suárez A, Ramos E, Gutiérrez C. Antibodies to ribosomal P proteins and hepatic damage in undifferentiated CTD. Ann Rheum Dis. 1996 Aug;55(8):562–563. [PMC free article] [PubMed]
  • Schneebaum AB, Singleton JD, West SG, Blodgett JK, Allen LG, Cheronis JC, Kotzin BL. Association of psychiatric manifestations with antibodies to ribosomal P proteins in systemic lupus erythematosus. Am J Med. 1991 Jan;90(1):54–62. [PubMed]
  • Casciola-Rosen LA, Anhalt G, Rosen A. Autoantigens targeted in systemic lupus erythematosus are clustered in two populations of surface structures on apoptotic keratinocytes. J Exp Med. 1994 Apr 1;179(4):1317–1330. [PMC free article] [PubMed]
  • Casciola-Rosen L, Rosen A, Petri M, Schlissel M. Surface blebs on apoptotic cells are sites of enhanced procoagulant activity: implications for coagulation events and antigenic spread in systemic lupus erythematosus. Proc Natl Acad Sci U S A. 1996 Feb 20;93(4):1624–1629. [PMC free article] [PubMed]
  • Koscec M, Koren E, Wolfson-Reichlin M, Fugate RD, Trieu E, Targoff IN, Reichlin M. Autoantibodies to ribosomal P proteins penetrate into live hepatocytes and cause cellular dysfunction in culture. J Immunol. 1997 Aug 15;159(4):2033–2041. [PubMed]
  • Winfield JB. Are anti-ribosomal P protein antibodies a type of anti-lymphocyte antibody? Clin Exp Immunol. 1997 Jul;109(1):1–3. [PMC free article] [PubMed]
  • Koren E, Reichlin MW, Koscec M, Fugate RD, Reichlin M. Autoantibodies to the ribosomal P proteins react with a plasma membrane-related target on human cells. J Clin Invest. 1992 Apr;89(4):1236–1241. [PMC free article] [PubMed]
  • Yoshio T, Masuyama J, Kano S. Antiribosomal P0 protein antibodies react with the surface of human umbilical vein endothelial cells. J Rheumatol. 1996 Jul;23(7):1311–1312. [PubMed]
  • Bordron A, Dueymes M, Levy Y, Jamin C, Ziporen L, Piette JC, Shoenfeld Y, Youinou P. Anti-endothelial cell antibody binding makes negatively charged phospholipids accessible to antiphospholipid antibodies. Arthritis Rheum. 1998 Oct;41(10):1738–1747. [PubMed]

Figures and Tables

Figure 1
Immunoblot analysis of serum samples from healthy donors on cytoplasmic extract of Raji cells resolved on 15% SDS-PAGE. Molecular weight markers are indicated in kilodaltons on the right.
Figure 2
Analysis of anti-P positive SLE sera (lanes 1-12) on a cytoplasmic blot. Immunoblot was interpreted as positive with concomitant lines corresponding to 38 kDa, 19 kDa, and 17 kDa bands. Control sera: (a) anti-P prototype serum; ...
Figure 3
Anti-P antibody detected by immunoblotting: sensitivity for systemic lupus erythematosus (SLE) and undifferentiated/overlap connective tissue diseases (UCTD) diagnosis and its specificity in healthy subjects and CTDs other than SLE or UCTD.
Figure 4
Association of anti-P and antiphospholipid (IgG anticardiolipin antibody (aCL), IgM aCL, lupus anticoagulant (LA)) responses in patients with systemic lupus erythematosus.
Figure 5
Immunoblot with anti-P serum from a patient with systemic lupus erythematosus and affinity purified fractions (material concentrated or filtrated on Centricon 50 tubes). (A) Anti-P serum after immunoabsorption on a negative control protein region ...

Articles from Annals of the Rheumatic Diseases are provided here courtesy of BMJ Group


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...