Logo of annrheumdAnnals of the Rheumatic DiseasesVisit this articleSubmit a manuscriptReceive email alertsContact usBMJ
Ann Rheum Dis. Jul 2005; 64(7): 1050–1055.
Published online Jan 7, 2005. doi:  10.1136/ard.2004.030643
PMCID: PMC1755548

Correlation of serum B lymphocyte stimulator and ß2 microglobulin with autoantibody secretion and systemic involvement in primary Sjögren's syndrome


Background: In primary Sjögren's syndrome (pSS), extraglandular involvement might result from more intense stimulation of autoreactive B cells. Thus markers of B cell activation could be useful in the clinical assessment of this disease.

Objective: To investigate the association of serum B lymphocyte stimulator (BLyS) and ß2 microglobulin with autoantibody production and extraglandular involvement in pSS.

Methods: Serum concentrations of BLyS and ß2 microglobulin were analysed in 177 patients with pSS according to the American–European consensus group criteria. Serum ß2 microglobulin was determined serially in 25 patients.

Results: Autoantibody secretion (presence of anti-SSA antibody alone or of both anti-SSA and anti-SSB) was associated with increased serum BLyS and ß2 microglobulin. No correlation was found between BLyS and ß2 microglobulin levels (p = 0.36). Serum concentrations of ß2 microglobulin and C reactive protein and positive anti-SSB antibody results were associated with extraglandular involvement on univariate analysis (p<10–4, p = 0.003, and p = 0.004, respectively). Serum ß2 microglobulin was also significantly increased in patients with extraglandular involvement without autoantibodies (mean (SD): 1.75 (0.7) v 1.39 (0.5) mg/l, p = 0.039). Multivariate analysis showed that extraglandular involvement was associated only with increased serum ß2 microglobulin (p = 0.035, odds ratio = 2.78 (95% confidence interval, 1.07 to 7.22)). Among the 25 patients who had serial determinations of serum ß2 microglobulin, the concentrations were increased in all those with disease flare and decreased in three following treatment. Serum BLyS, gamma globulin, IgG, and rheumatoid factor levels were not associated with features of systemic involvement.

Conclusions: Serum ß2 microglobulin and BLyS reflect B cell activation in different ways in pSS. Serum ß2 microglobulin assessment could be helpful as an activity marker in pSS.

Full Text

The Full Text of this article is available as a PDF (95K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Jonsson Roland, Gordon Tom P, Konttinen Yrjö T. Recent advances in understanding molecular mechanisms in the pathogenesis and antibody profile of Sjögren's syndrome. Curr Rheumatol Rep. 2003 Aug;5(4):311–316. [PubMed]
  • Kassan SS, Thomas TL, Moutsopoulos HM, Hoover R, Kimberly RP, Budman DR, Costa J, Decker JL, Chused TM. Increased risk of lymphoma in sicca syndrome. Ann Intern Med. 1978 Dec;89(6):888–892. [PubMed]
  • Ioannidis John P A, Vassiliou Vassilios A, Moutsopoulos Haralampos M. Long-term risk of mortality and lymphoproliferative disease and predictive classification of primary Sjögren's syndrome. Arthritis Rheum. 2002 Mar;46(3):741–747. [PubMed]
  • Martin T, Weber JC, Levallois H, Labouret N, Soley A, Koenig S, Korganow AS, Pasquali JL. Salivary gland lymphomas in patients with Sjögren's syndrome may frequently develop from rheumatoid factor B cells. Arthritis Rheum. 2000 Apr;43(4):908–916. [PubMed]
  • Harley JB, Alexander EL, Bias WB, Fox OF, Provost TT, Reichlin M, Yamagata H, Arnett FC. Anti-Ro (SS-A) and anti-La (SS-B) in patients with Sjögren's syndrome. Arthritis Rheum. 1986 Feb;29(2):196–206. [PubMed]
  • Bjorkman PJ, Parham P. Structure, function, and diversity of class I major histocompatibility complex molecules. Annu Rev Biochem. 1990;59:253–288. [PubMed]
  • Bianchi C, Donadio C, Tramonti G, Consani C, Lorusso P, Rossi G. Reappraisal of serum beta2-microglobulin as marker of GFR. Ren Fail. 2001 May-Jul;23(3-4):419–429. [PubMed]
  • Bataille R, Grenier J, Sany J. Beta-2-microglobulin in myeloma: optimal use for staging, prognosis, and treatment--a prospective study of 160 patients. Blood. 1984 Feb;63(2):468–476. [PubMed]
  • Seymour John F, Pro Barbara, Fuller Lillian M, Manning John T, Hagemeister Fredrick B, Romaguera Jorge, Rodriguez Maria A, Ha Chul S, Smith Terry L, Ayala Ana, et al. Long-term follow-up of a prospective study of combined modality therapy for stage I-II indolent non-Hodgkin's lymphoma. J Clin Oncol. 2003 Jun 1;21(11):2115–2122. [PubMed]
  • Chronowski Gregory M, Wilder Richard B, Tucker Susan L, Ha Chul S, Sarris Andreas H, Hagemeister Fredrick B, Barista Ibrahim, Hess Mark A, Cabanillas Fernando, Cox James D. An elevated serum beta-2-microglobulin level is an adverse prognostic factor for overall survival in patients with early-stage Hodgkin disease. Cancer. 2002 Dec 15;95(12):2534–2538. [PubMed]
  • Lifson AR, Hessol NA, Buchbinder SP, O'Malley PM, Barnhart L, Segal M, Katz MH, Holmberg SD. Serum beta 2-microglobulin and prediction of progression to AIDS in HIV infection. Lancet. 1992 Jun 13;339(8807):1436–1440. [PubMed]
  • Morfeldt-Månson J, Julander I, von Stedingk LV, Wasserman J, Nilsson B. Elevated serum beta-2-microglobulin--a prognostic marker for development of AIDS among patients with persistent generalized lymphadenopathy. Infection. 1988 Mar-Apr;16(2):109–110. [PubMed]
  • Michalski JP, Daniels TE, Talal N, Grey HM. Beta2 microglobulin and lymphocytic infiltration in Sjögren's syndrome. N Engl J Med. 1975 Dec 11;293(24):1228–1231. [PubMed]
  • Talal N, Grey HM, Zvaifler N, Michalski JP, Daniels TE. Elevated salivary and synovial fluid beta2-microglobulin in Sjogren's syndrome and rheumatoid arthritis. Science. 1975 Mar 28;187(4182):1196–1198. [PubMed]
  • Maddali Bongi S, Campana G, D'Agata A, Palermo C, Bianucci G. The diagnosis value of beta 2-microglobulin and immunoglobulins in primary Sjögren's syndrome. Clin Rheumatol. 1995 Mar;14(2):151–156. [PubMed]
  • Castro José, Jiménez-Alonso Juan, Sabio José Mario, Rivera-Cívico Francisco, Martín-Armada María, Rodríguez Miguel Angel, Jáimez Laura, Castillo María Jesús, Sánchez-Román Julio. Salivary and serum beta2-microglobulin and gamma-glutamyl-transferase in patients with primary Sjögren syndrome and Sjögren syndrome secondary to systemic lupus erythematosus. Clin Chim Acta. 2003 Aug;334(1-2):225–231. [PubMed]
  • Moore PA, Belvedere O, Orr A, Pieri K, LaFleur DW, Feng P, Soppet D, Charters M, Gentz R, Parmelee D, et al. BLyS: member of the tumor necrosis factor family and B lymphocyte stimulator. Science. 1999 Jul 9;285(5425):260–263. [PubMed]
  • Schneider P, MacKay F, Steiner V, Hofmann K, Bodmer JL, Holler N, Ambrose C, Lawton P, Bixler S, Acha-Orbea H, et al. BAFF, a novel ligand of the tumor necrosis factor family, stimulates B cell growth. J Exp Med. 1999 Jun 7;189(11):1747–1756. [PMC free article] [PubMed]
  • Mackay Fabienne, Browning Jeffrey L. BAFF: a fundamental survival factor for B cells. Nat Rev Immunol. 2002 Jul;2(7):465–475. [PubMed]
  • Mackay F, Woodcock SA, Lawton P, Ambrose C, Baetscher M, Schneider P, Tschopp J, Browning JL. Mice transgenic for BAFF develop lymphocytic disorders along with autoimmune manifestations. J Exp Med. 1999 Dec 6;190(11):1697–1710. [PMC free article] [PubMed]
  • Cheema GS, Roschke V, Hilbert DM, Stohl W. Elevated serum B lymphocyte stimulator levels in patients with systemic immune-based rheumatic diseases. Arthritis Rheum. 2001 Jun;44(6):1313–1319. [PubMed]
  • Mariette X, Roux S, Zhang J, Bengoufa D, Lavie F, Zhou T, Kimberly R. The level of BLyS (BAFF) correlates with the titre of autoantibodies in human Sjögren's syndrome. Ann Rheum Dis. 2003 Feb;62(2):168–171. [PMC free article] [PubMed]
  • Vitali C, Bombardieri S, Jonsson R, Moutsopoulos HM, Alexander EL, Carsons SE, Daniels TE, Fox PC, Fox RI, Kassan SS, et al. Classification criteria for Sjögren's syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis. 2002 Jun;61(6):554–558. [PMC free article] [PubMed]
  • Davidson BK, Kelly CA, Griffiths ID. Primary Sjögren's syndrome in the North East of England: a long-term follow-up study. Rheumatology (Oxford) 1999 Mar;38(3):245–253. [PubMed]
  • Shields MJ, Kubota R, Hodgson W, Jacobson S, Biddison WE, Ribaudo RK. The effect of human beta2-microglobulin on major histocompatibility complex I peptide loading and the engineering of a high affinity variant. Implications for peptide-based vaccines. J Biol Chem. 1998 Oct 23;273(43):28010–28018. [PubMed]
  • Xie Jin, Yi Qing. Beta2-microglobulin as a potential initiator of inflammatory responses. Trends Immunol. 2003 May;24(5):228–230. [PubMed]
  • Xie Jin, Wang Ying, Freeman Muta E, 3rd, Barlogie Bart, Yi Qing. Beta 2-microglobulin as a negative regulator of the immune system: high concentrations of the protein inhibit in vitro generation of functional dendritic cells. Blood. 2003 May 15;101(10):4005–4012. [PubMed]
  • Mori M, Terui Y, Tanaka M, Tomizuka H, Mishima Y, Ikeda M, Kasahara T, Uwai M, Ueda M, Inoue R, et al. Antitumor effect of beta2-microglobulin in leukemic cell-bearing mice via apoptosis-inducing activity: activation of caspase-3 and nuclear factor-kappaB. Cancer Res. 2001 Jun 1;61(11):4414–4417. [PubMed]
  • Schirmbeck R, Thoma S, Reimann J. Processing of exogenous hepatitis B surface antigen particles for Ld-restricted epitope presentation depends on exogenous beta2-microglobulin. Eur J Immunol. 1997 Dec;27(12):3471–3484. [PubMed]
  • Lavie Frédéric, Miceli-Richard Corinne, Quillard Jeanine, Roux Sophie, Leclerc Philippe, Mariette Xavier. Expression of BAFF (BLyS) in T cells infiltrating labial salivary glands from patients with Sjögren's syndrome. J Pathol. 2004 Apr;202(4):496–502. [PubMed]
  • Stohl William, Metyas Samy, Tan Soon-Min, Cheema Gurtej S, Oamar Bonifacia, Xu Dong, Roschke Viktor, Wu Youmei, Baker Kevin P, Hilbert David M. B lymphocyte stimulator overexpression in patients with systemic lupus erythematosus: longitudinal observations. Arthritis Rheum. 2003 Dec;48(12):3475–3486. [PubMed]
  • Fox RI, Chan E, Benton L, Fong S, Friedlaender M, Howell FV. Treatment of primary Sjögren's syndrome with hydroxychloroquine. Am J Med. 1988 Oct 14;85(4A):62–67. [PubMed]
  • Fox RI, Dixon R, Guarrasi V, Krubel S. Treatment of primary Sjögren's syndrome with hydroxychloroquine: a retrospective, open-label study. Lupus. 1996 Jun;5 (Suppl 1):S31–S36. [PubMed]
  • Tishler M, Yaron I, Shirazi I, Yaron M. Hydroxychloroquine treatment for primary Sjögren's syndrome: its effect on salivary and serum inflammatory markers. Ann Rheum Dis. 1999 Apr;58(4):253–256. [PMC free article] [PubMed]
  • Alexander EL, Arnett FC, Provost TT, Stevens MB. Sjögren's syndrome: association of anti-Ro(SS-A) antibodies with vasculitis, hematologic abnormalities, and serologic hyperreactivity. Ann Intern Med. 1983 Feb;98(2):155–159. [PubMed]
  • Gottenberg Jacques-Eric, Busson Marc, Loiseau Pascale, Cohen-Solal Julien, Lepage Virginia, Charron Dominique, Sibilia Jean, Mariette Xavier. In primary Sjögren's syndrome, HLA class II is associated exclusively with autoantibody production and spreading of the autoimmune response. Arthritis Rheum. 2003 Aug;48(8):2240–2245. [PubMed]
  • Wahren M, Tengnér P, Gunnarsson I, Lundberg I, Hedfors E, Ringertz NR, Pettersson I. Ro/SS-A and La/SS-B antibody level variation in patients with Sjögren's syndrome and systemic lupus erythematosus. J Autoimmun. 1998 Feb;11(1):29–38. [PubMed]
  • Pertovaara M, Korpela M, Pasternack A. Factors predictive of renal involvement in patients with primary Sjögren's syndrome. Clin Nephrol. 2001 Jul;56(1):10–18. [PubMed]
  • Lahdensuo A, Korpela M. Pulmonary findings in patients with primary Sjögren's syndrome. Chest. 1995 Aug;108(2):316–319. [PubMed]
  • Hatron PY, Wallaert B, Gosset D, Tonnel AB, Gosselin B, Voisin C, Devulder B. Subclinical lung inflammation in primary Sjögren's syndrome. Relationship between bronchoalveolar lavage cellular analysis findings and characteristics of the disease. Arthritis Rheum. 1987 Nov;30(11):1226–1231. [PubMed]
  • Pertovaara M, Pukkala E, Laippala P, Miettinen A, Pasternack A. A longitudinal cohort study of Finnish patients with primary Sjögren's syndrome: clinical, immunological, and epidemiological aspects. Ann Rheum Dis. 2001 May;60(5):467–472. [PMC free article] [PubMed]
  • Oxholm P. Primary Sjögren's syndrome--clinical and laboratory markers of disease activity. Semin Arthritis Rheum. 1992 Oct;22(2):114–126. [PubMed]
  • Asmussen KH, Bowman SJ. Outcome measures in Sjögren's syndrome. Rheumatology (Oxford) 2001 Oct;40(10):1085–1088. [PubMed]

Figures and Tables

Figure 1
 Serum ß2 microglobulin (ß2m) and B lymphocyte stimulator (BLys) concentrations according to the presence of anti-SSA/SSB antibodies.
Figure 2
 ß2 microglobulin concentrations in patients with extraglandular involvement and in patients with glandular involvement only.
Figure 3
 Mean serum ß2 microglobulin value in 154 patients with primary Sjögren's syndrome according to the presence of extraglandular involvement and of anti-SSA/SSB antibodies.

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...