References

1.Capriello P, Barale E, Cappelli N, Lupo S, Teti G. Sjogren’s syndrome: clinical, cytological, histological and colposcopic aspects in women. Clin Exp Obstet Gynecol. 1988;15:9–12.

2.Skopouli FN, Papanikolaou S, Malamou-Mitsi V, Papanikolaou N, Moutsopoulos HM. Obstetric and gynaecological profile in patients with primary Sjogren’s syndrome. Ann Rheum Dis. 1994;53:569–73.

3.Mulherin DM, Sheeran TP, Kumararatne DS, Speculand B, Luesley D, Situnayake RD. Sjogren’s syndrome in women presenting with chronic dyspareunia. Br J Obstet Gynaecol. 1997;104:1019–23.

4.Cirpan T, Guliyeva A, Onder G, Terek MC, Ozsaran A, Kabasakal Y, et al. Comparison of human papillomavirus testing and cervical cytology with colposcopic examination and biopsy in cervical cancer screening in a cohort of patients with Sjogren’s syndrome. Eur J Gynaecol Oncol. 2007;28:302–6.

5.Marchesoni D, Mozzanega B, De Sandre P, Romagnolo C, Gambari PF, Maggino T. Gynaecological aspects of primary Sjogren’s syndrome. Eur J Obstet Gynecol Reprod Biol. 1995;63:49–53.

6.Haga HJ, Gjesdal CG, Irgens LM, Ostensen M. Reproduction and gynaecological manifestations in women with primary Sjogren’s syndrome: a case-control study. Scand J Rheumatol. 2005;34:45–8.

7.Boh EE. Neonatal lupus erythematosus. Clin Dermatol. 2004;22:125–8.

8.Brucato A, Cimaz R, Caporali R, Ramoni V, Buyon J. Pregnancy outcomes in patients with autoimmune diseases and anti-Ro/SSA antibodies. Clin Rev Allergy Immunol. 2011;40(1): 27–41.

9.Buyon JP, Brucato A, Friedman DM. What’s in a name? Ann Rheum Dis. 2008;67:732; discussion 732.

10. Routsias JG, Tzioufas AG. Sjogren’s syndrome – study of autoantigens and autoantibodies. Clin Rev Allergy Immunol. 2007;32:238–51.

11. Vitali C, Bombardieri S, Jonsson R, Moutsopoulos HM, Alexander EL, Carsons SE, et al. Classification criteria for Sjogren’s syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis. 2002;61:554–8.

12. Siren MK, Julkunen H, Kaaja R. The increasing incidence of isolated congenital heart block in Finland. J Rheumatol. 1998;25:1862–4.

13. Michaelsson M, Engle MA. Congenital complete heart block: an international study of the natural history. Cardiovasc Clin. 1972;4:85–101.

14. Lee LA. Neonatal lupus erythematosus. J Invest Dermatol. 1993;100:9S–13S.

15. Sontheimer RD, Maddison PJ, Reichlin M, Jordon RE, Stastny P, Gilliam JN. Serologic and HLA associations in subacute cutaneous lupus erythematosus, a clinical subset of lupus erythematosus. Ann Intern Med. 1982;97:664–71.

16. Sontheimer RD, McCauliffe DP. Pathogenesis of anti-Ro/SS-A autoantibody-associated cutaneous lupus erythematosus. Dermatol Clin. 1990;8:751–8.

17. Watson R, Kang JE, May M, Hudak M, Kickler T, Provost TT. Thrombocytopenia in the neonatal lupus syndrome. Arch Dermatol. 1988;124:560–3.

18. Kanagasegar S, Cimaz R, Kurien BT, Brucato A, Scofield RH. Neonatal lupus manifests as isolated neutropenia and mildly abnormal liver functions. J Rheumatol. 2002;29:187–91.

19. Laxer RM, Roberts EA, Gross KR, Britton JR, Cutz E, Dimmick J, et al. Liver disease in neonatal lupus erythematosus. J Pediatr. 1990;116:238–42.

20. Cimaz R, Spence DL, Hornberger L, Silverman ED. Incidence and spectrum of neonatal lupus erythematosus: a prospective study of infants born to mothers with anti-Ro autoantibodies. J Pediatr. 2003;142:678–83.

21. Ross G, Sammaritano L, Nass R, Lockshin M. Effects of mothers’ autoimmune disease during pregnancy on learning disabilities and hand preference in their children. Arch Pediatr Adolesc Med. 2003;157:397–402.

22. Boros CA, Spence D, Blaser S, Silverman ED. Hydrocephalus and macrocephaly: new manifestations of neonatal lupus erythematosus. Arthritis Rheum. 2007;57:261–6.

23. Schmidt KG, Ulmer HE, Silverman NH, Kleinman CS, Copel JA. Perinatal outcome of fetal complete atrioventricular block: a multicenter experience. J Am Coll Cardiol. 1991;17: 1360–6.

24. Fesslova V, Vignati G, Brucato A, De Sanctis M, Butera G, Pisoni MP, et al. The impact of treatment of the fetus by maternal therapy on the fetal and postnatal outcomes for fetuses diagnosed with isolated complete atrioventricular block. Cardiol Young. 2009;19:282–90.

25. Moak JP, Barron KS, Hougen TJ, Wiles HB, Balaji S, Sreeram N, et al. Congenital heart block: development of late-onset cardiomyopathy, a previously underappreciated sequela. J Am Coll Cardiol. 2001;37:238–42.

26. Udink ten Cate FE, Breur JM, Cohen MI, Boramanand N, Kapusta L, Crosson JE, et al. Dilated cardiomyopathy in isolated congenital complete atrioventricular block: early and long-term risk in children. J Am Coll Cardiol. 2001;37:1129–34.

27. Nield LE, Silverman ED, Smallhorn JF, Taylor GP, Mullen JB, Benson LN, et al. Endocardial fibroelastosis associated with maternal anti-Ro and anti-La antibodies in the absence of atrioventricular block. J Am Coll Cardiol. 2002;40:796–802.

28. Brucato A, Cimaz R, Catelli L, Meroni P. Anti-Ro-associated sinus bradycardia in newborns. Circulation. 2000;102:E88–9.

29. Cimaz R, Stramba-Badiale M, Brucato A, Catelli L, Panzeri P, Meroni PL. QT interval prolongation in asymptomatic anti-SSA/Ro-positive infants without congenital heart block. Arthritis Rheum. 2000;43:1049–53.

30. Costedoat-Chalumeau N, Amoura Z, Lupoglazoff JM, Huong DL, Denjoy I, Vauthier D, et al. Outcome of pregnancies in patients with anti-SSA/Ro antibodies: a study of 165 pregnancies, with special focus on electrocardiographic variations in the children and comparison with a control group. Arthritis Rheum. 2004;50:3187–94.

31. Friedman DM, Kim MY, Copel JA, Davis C, Phoon CK, Glickstein JS, et al. Utility of cardiac monitoring in fetuses at risk for congenital heart block: the PR Interval and Dexamethasone Evaluation (PRIDE) prospective study. Circulation. 2008;117:485–93.

32. Cuneo BF, Strasburger JF, Niksch A, Ovadia M, Wakai RT. An expanded phenotype of maternal SSA/SSB antibody-associated fetal cardiac disease. J Matern Fetal Neonatal Med. 2009;22:233–8.

33. Waltuck J, Buyon JP. Autoantibody-associated congenital heart block: outcome in mothers and children. Ann Intern Med. 1994;120:544–51.

34. Press J, Uziel Y, Laxer RM, Luy L, Hamilton RM, Silverman ED. Long-term outcome of mothers of children with complete congenital heart block. Am J Med. 1996;100:328–32.

35. Rivera TL, Izmirly PM, Birnbaum BK, Byrne P, Brauth JB, Katholi M, et al. Disease progression in mothers of children enrolled in the Research Registry for Neonatal Lupus. Ann Rheum Dis. 2009;68:828–35.

36. Brucato A, Gasparini M, Vignati G, Riccobono S, De Juli E, Quinzanini M, et al. Isolated congenital complete heart block: longterm outcome of children and immunogenetic study. J Rheumatol. 1995;22:541–3.

37. Martin V, Lee LA, Askanase AD, Katholi M, Buyon JP. Long-term followup of children with neonatal lupus and their unaffected siblings. Arthritis Rheum. 2002;46:2377–83.

38. Sonesson SE, Salomonsson S, Jacobsson LA, Bremme K, Wahren-Herlenius M. Signs of firstdegree heart block occur in one-third of fetuses of pregnant women with anti-SSA/Ro 52-kd antibodies. Arthritis Rheum. 2004;50:1253–61.

39.Rein AJ, Mevorach D, Perles Z, Gavri S, Nadjari M, Nir A, et al. Early diagnosis and treatment of atrioventricular block in the fetus exposed to maternal anti-SSA/Ro-SSB/La antibodies: a prospective, observational, fetal kinetocardiogram-based study. Circulation. 2009;119:1867–72.

40. Brucato A, Frassi M, Franceschini F, Cimaz R, Faden D, Pisoni MP, et al. Risk of congenital complete heart block in newborns of mothers with anti-Ro/SSA antibodies detected by counterimmunoelectrophoresis: a prospective study of 100 women. Arthritis Rheum. 2001;44: 1832–5.

41. Gladman G, Silverman ED, Yuk L, Luy L, Boutin C, Laskin C, et al. Fetal echocardiographic screening of pregnancies of mothers with anti-Ro and/or anti-La antibodies. Am J Perinatol. 2002;19:73–80.

42. Gerosa M, Cimaz R, Stramba-Badiale M, Goulene K, Meregalli E, Trespidi L, et al. Electrocardiographic abnormalities in infants born from mothers with autoimmune diseases – a multicentre prospective study. Rheumatology (Oxford). 2007;46:1285–9.

43. Gordon P, Khamashta MA, Rosenthal E, Simpson JM, Sharland G, Brucato A, et al. Anti52 kDa Ro, anti-60 kDa Ro, and anti-La antibody profiles in neonatal lupus. J Rheumatol. 2004;31:2480–7.

44. Salomonsson S, Sonesson SE, Ottosson L, Muhallab S, Olsson T, Sunnerhagen M, et al. Ro/ SSA autoantibodies directly bind cardiomyocytes, disturb calcium homeostasis, and mediate congenital heart block. J Exp Med. 2005;201:11–7.

45. Izmirly PM, Llanos C, Lee LA, Askanase A, Kim MY, Buyon JP. Cutaneous manifestations of neonatal lupus and risk of subsequent congenital heart block. Arthritis Rheum. 2010;62: 1153–7.

46. Spence D, Hornberger L, Hamilton R, Silverman ED. Increased risk of complete congenital heart block in infants born to women with hypothyroidism and anti-Ro and/or anti-La antibodies. J Rheumatol. 2006;33:167–70.

47. Llanos C, Izmirly PM, Katholi M, Clancy RM, Friedman DM, Kim MY, et al. Recurrence rates of cardiac manifestations associated with neonatal lupus and maternal/fetal risk factors. Arthritis Rheum. 2009;60:3091–7.

48. Strandberg L, Winqvist O, Sonesson SE, Mohseni S, Salomonsson S, Bremme K, et al. Antibodies to amino acid 200–239 (p200) of Ro52 as serological markers for the risk of developing congenital heart block. Clin Exp Immunol. 2008;154:30–7.

49. Stea EA, Routsias JG, Clancy RM, Buyon JP, Moutsopoulos HM, Tzioufas AG. Anti-La/SSB antiidiotypic antibodies in maternal serum: a marker of low risk for neonatal lupus in an offspring. Arthritis Rheum. 2006;54:2228–34.

50. James TN. Normal and abnormal consequences of apoptosis in the human heart: from postnatal morphogenesis to paroxysmal arrhythmias. Circulation. 1994;90:556–73.

51. Miranda-Carus ME, Askanase AD, Clancy RM, Di Donato F, Chou TM, Libera MR, et al. Anti-SSA/Ro and anti-SSB/La autoantibodies bind the surface of apoptotic fetal cardiocytes and promote secretion of TNF-alpha by macrophages. J Immunol. 2000;165:5345–51.

52. Clancy RM, Buyon JP. Clearance of apoptotic cells: TGF-beta in the balance between inflammation and fibrosis. J Leukoc Biol. 2003;74:959–60.

53.Clancy RM, Neufing PJ, Zheng P, O’Mahony M, Nimmerjahn F, Gordon TP, et al. Impaired clearance of apoptotic cardiocytes is linked to anti-SSA/Ro and -SSB/La antibodies in the pathogenesis of congenital heart block. J Clin Invest. 2006;116:2413–22.

54.Clancy RM, Backer CB, Yin X, Kapur RP, Molad Y, Buyon JP. Cytokine polymorphisms and

histologic expression in autopsy studies: contribution of TNF-alpha and TGF-beta 1 to the pathogenesis of autoimmune-associated congenital heart block. J Immunol. 2003;171:3253–61.

55. Jaeggi ET, Fouron JC, Silverman ED, Ryan G, Smallhorn J, Hornberger LK. Transplacental fetal treatment improves the outcome of prenatally diagnosed complete atrioventricular block without structural heart disease. Circulation. 2004;110:1542–8.

56. Theander E, Brucato A, Gudmundsson S, Salomonsson S, Wahren-Herlenius M, Manthorpe R. Primary Sjogren’s syndrome – treatment of fetal incomplete atrioventricular block with dexamethasone. J Rheumatol. 2001;28:373–6.

57. Saleeb S, Copel J, Friedman D, Buyon JP. Comparison of treatment with fluorinated glucocorticoids to the natural history of autoantibody-associated congenital heart block: retrospective review of the research registry for neonatal lupus. Arthritis Rheum. 1999;42:2335–45.

58. Lopes LM, Tavares GM, Damiano AP, Lopes MA, Aiello VD, Schultz R, et al. Perinatal outcome of fetal atrioventricular block: one-hundred-sixteen cases from a single institution. Circulation. 2008;118:1268–75.

59. Breur JM, Visser GH, Kruize AA, Stoutenbeek P, Meijboom EJ. Treatment of fetal heart block with maternal steroid therapy: case report and review of the literature. Ultrasound Obstet Gynecol. 2004;24:467–72.

60. Brucato A, Astori MG, Cimaz R, Villa P, Li Destri M, Chimini L, et al. Normal neuropsychological development in children with congenital complete heart block who may or may not be exposed to high-dose dexamethasone in utero. Ann Rheum Dis. 2006;65:1422–6.

61. Kaaja R, Julkunen H. Prevention of recurrence of congenital heart block with intravenous immunoglobulin and corticosteroid therapy: comment on the editorial by Buyon et al. Arthritis Rheum. 2003;48:280–1; author reply 281–282.

62. Kaaja R, Julkunen H, Ammala P, Teppo AM, Kurki P. Congenital heart block: successful prophylactic treatment with intravenous gamma globulin and corticosteroid therapy. Am J Obstet Gynecol. 1991;165:1333–4.

63. Pisoni CN, Brucato A, Ruffatti A, Espinosa G, Cervera R, Belmonte-Serrano M, et al. Failure of intravenous immunoglobulin to prevent congenital heart block: findings of a multicenter, prospective, observational study. Arthritis Rheum. 2010;62:1147–52.

64. Friedman DM, Llanos C, Izmirly PM, Brock B, Byron J, Copel J, et al. Evaluation of fetuses in a study of intravenous immunoglobulin as preventive therapy for congenital heart block: results of a multicenter, prospective, open-label clinical trial. Arthritis Rheum. 2010;62: 1138–46.

65. Matsubara S, Morimatsu Y, Shiraishi H, Kuwata T, Ohkuchi A, Izumi A, et al. Fetus with heart failure due to congenital atrioventricular block treated by maternally administered ritodrine. Arch Gynecol Obstet. 2008;278:85–8.

66. Izmirly PM, Kim MY, Llanos C, Le PU, Guerra MM, Askanase AD, et al. Evaluation of the risk of anti-SSA/Ro-SSB/La antibody-associated cardiac manifestations of neonatal lupus in fetuses of mothers with systemic lupus erythematosus exposed to hydroxychloroquine. Ann Rheum Dis. 2010;69(10):1827–30.

67. Routsias JG, Kyriakidis NC, Friedman DM, Llanos C, Clancy R, Moutsopoulos HM, Buyon J, Tzioufas AG. Association of idiotypic/anti-idiotypic antibody ratio with therapeutic response of IVIG in the prevention of recurrent autoimmune associated congenital heart block. Arthritis Rheum. 2011 May 25. doi: 10.1002/art.30464. [Epub ahead of print]

Chapter 25

Laboratory Abnormalities

in Primary Sjögren’s Syndrome

Pilar Brito-Zerón, Roberto Pérez-Alvarez, Marta Pérez-de-Lis, Carmen Hidalgo-Tenorio, and Manuel Ramos-Casals

Contents

P. Brito-Zerón • M. Ramos-Casals (*)

Sjögren Syndrome Research Group (AGAUR), Laboratory of Autoimmune Diseases Josep Font, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Department of Autoimmune Diseases, Hospital Clínic, Barcelona, Spain

R. Pérez-Alvarez • M. Pérez-de-Lis

Department of Internal Medicine, Hospital Meixoeiro, Vigo, Spain

C. Hidalgo-Tenorio

Department of Internal Medicine, Hospital Virgen de las Nieves, Granada, Spain