Endocrine Manifestations of Systemic Autoimmune Diseases

319 Pages·2008·6.185 MB·English

by  Sara E. Walker and Luis J. Jara (Eds.)

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Preface
This issue of the Handbook of Systemic Autoimmune Diseases addresses endocrine manifestations of
systemicautoimmunediseases.Neuroendocrineimmunologyhasbeendevelopedinthelastyearsthanksto
the activities of different associations such as the International Society for Neuroimmunomodulation
(ISNIM), the Study Group on Endocrine Immunology at the American College of Rheumatology (ACR),
and the Study Group on Neuroendocrine Immunology of the Rheumatic Diseases (NEIRD) at the
European League against Reumatism (EULAR) and others.
The early chapters of the issue will introduce the background of genetic expression, within which
reciprocal regulatory networks enhance communication between neuroimmune and endocrine systems,
resulting in biologic reactions that lead to clinical syndromes.
The major themes of this volume are clinical and therapeutic approaches to recognizing and treating
systemicautoimmunediseasesthatinvolvetheendocrinesystem.Inparticular,immunemechanismsleading
topathologicaldamageanddysfunctionofadrenals,gonads,thyroid,pituitary,andpancreasarediscussed
in well-balanced reviews written by leading authors.
Old and new therapies are presented and evaluated on the light of their more recent effects on the
neuroimmune endocrine network, and reviews of the immunologic actions of vitamin D and TNF-a
blockers are included.
We hope that readers will appreciate the concept of interplay between different systems. In human
autoimmunediseases,availableevidenceindicatesthatthere isaprolongedpreclinical phase,lasting years,
during which the above-mentioned systems may play a crucial role before symptomatic disease is evident.
The role of the adrenal glands, gonadal steroids, and pregnancy as modulators of the immune response
willrepresentsomeofthetopicsinautoimmunitythatarediscussed.Weareconvincedthatreaderswillfind
newandprovocativethoughtsinthisissue,leadingtostimulationoffurtherinterestingresearchinthisarea.
Finally, we extend our great appreciation to all the authors of this issue for their updated and expert
contributions.
Maurizio Cutolo
v
Series Editor
Prof. Ronald A. Asherson
Professor Ronald A. Asherson, MD, FACP, MD (Hon) (London), FCP (SA), FACR, Dip O&G (Hon) is
Professor of Immunology (Hon), at the School of Pathology, University of the Witwatersrand, as well as
being Consultant Rheumatologist at the Rosebank Clinic in Johannesburg, South Africa. He is also a
Professor at the Systemic Autoimmune Diseases Unit at the Hospital Clinic, Barcelona, Spain where he
regularly visits and coordinates research projects.
Professor Asherson qualified in Medicine at the University of Cape Town in 1957 and, after completing
his internship, became H/P to Professor Sir Christopher Booth at the Hammersmith Hospital, London in
1960. In 1961, he accepted a Fellowship at the Columbia Presbyterian Hospital in New York, returning in
1962 to become Registrar and then Senior Registrar till 1964 at Groote Schuur Hospital in Cape Town.
After10yearsasaClinicalTutorintheDepartmentofMedicine,hereturnedtotheUnitedStatesandwas
appointed as Assistant Clinical Professor of Medicine at the New York Hospital-Cornell Medical Centre
underthelateProfessorHenryHeinemann.From1981to1986,hewasassociated withtheRheumatology
DepartmentattheRoyalPostgraduateMedicalSchoolofLondon.Itwasatthattimethathedevelopedhis
interest in Connective Tissue Diseases and Antiphospholipid Antibodies.
In1986,hemovedtotheRayne InstituteandSt.Thomas’HospitalinLondon,wherehewasappointed
Honorary Consultant Physician and Senior Research Fellow. In 1991, he took a sabbatical at St. Luke’s
Roosevelt Hospital Center in New York, working with Professor Robert Lahita. In 1992, he returned to
South Africa for private practice in Johannesburg.
In 1998, he was elected as Fellow of the American College of Physicians (FACP) as well as a Founding
FellowoftheAmericanCollegeofRheumatology(FACR).From1988to1991,heservedontheCouncilof
the Royal Society of Medicine in London. In 1992, he was co-winner of the European League Against
Rheumatism (EULAR) Prize and in 1993 was the co-recipient of the International League Against
Rheumatism(ILAR)Prize,bothforhisresearchonantiphospholipidantibodies.In1994,hewaselecteda
Fellow of the Royal College of Physicians (FRCP) of London. In 2002, he was awarded an Honorary
Doctorate in Medicine from the University of Pleven in Bulgaria.
ProfessorAsherson has been an invited speaker atmany universities and Internationalconferences both
in the USA and in Europe. He is the author of more than 300 papers on connective tissue diseases and
has contributed to more than 30 textbooks of medicine, rheumatology, and surgery, besides co-edited
‘‘Problems in the Rheumatic Diseases’’, the ‘‘Phospholipid Binding Antibodies’’, and two editions of
‘‘TheAntiphospholipidSyndrome’’and‘‘VascularManifestationsoftheSystemicAutoimmuneDiseases’’.
He is currently engaged in research on connective tissue diseases, particularly on the antiphsopholipid
syndrometogetherwithcolleaguesintheUSA,Spain,France,andIsraelandisinclinicalpracticeinSouth
Africa.In1999,hewastheco-recipientoftheJuanVivancosPrizeinSpainandin2003wastheco-recipient
of the Abbott Prize, awarded at the European League Against Rheumatism (EULAR) International
Meeting, held in Lisbon, Portugal.
His original description of the ‘‘Catastrophic Antiphospholipid Syndrome’’ and the publishing of more
than40papersonthisnewdiseasewasrewardedbytheattachmentoftheeponym‘‘Asherson’sSyndrome’’
to this condition at the November 2002 International Phospholipid Conference held in Sicily. He has
established the first International Committee to study survivors of this syndrome.
Heiscurrentlyeditingaseriesof12volumesentitled‘‘TheHandbookofSystemicAutoimmuneDisease’’
(Elsevier) and in September of 2003 was Co-Chairman of the First Latin American Congress on
Autoimmunity,heldintheGalapagosIslands,Ecuador.Heco-chairedandparticipatedinaSessionatthe
Milan Conference on ‘‘Heart, Rheumatism and Autoimmunity’’ held in February 2004.
vii
viii SeriesEditor
He was awarded an Honorary Fellowship of the Slovakian Rheumatology Association in 2005.
In2007,hewasawardedanHonoraryLifeMembershipoftheSouthAfricanRheumatologyAssociation.
HechairedacombinedsessionofCzechandSlovakianRheumatologistsinBratislava,Slovakiadevotedto
the Catastrophic Antiphospholipid Syndrome. In late 2007, he was awarded Honorary Membership and a
Diploma as well as the medal of the Russian Society of Obstetrics and Gynaecology for his outstanding
contributions to clinical medicine, and the discovery and study of the catastrophic antiphsopholipid
syndrome.
Volume Editors
Sara E. Walker
Dr. Sara E. Walker was trained in rheumatology at the Rackham Arthritis Unit at the University of
Michigan. She is currently Professor Emeritus of Internal Medicine in the Division of Immunology and
Rheumatology at the University of Missouri. She has a longstanding research interest in the effects of
peptidehormonesonSLE.Dr.WalkerisaMasteroftheAmericanCollegeofRheumatologyandaMaster
oftheAmericanCollegeofPhysicians.ShewasPresidentoftheAmericanCollegeofPhysicians,from2002
to 2003.
Luis J. Jara
Dr.LuisJ.JarawasborninPeru´ in1948.HelivedinMexicosince1982.HereceivedhisMDdegreefrom
the National University ‘‘Federico Villareal’’, Faculty of Medicine in Lima, Peru´ in 1975. He trained in
internal medicine at the National University of San Marcos, Faculty of Medicine ‘‘San Fernando’’ from
1975to1978.From1980to1982,heobtainedascholarshipfromtheInstitutoMexicanodelSeguroSocial
tobetrainedinrheumatologyattheHospitaldeEspecialidadesCentroMe´dicoLaRaza.Hewasapproved
by the Rheumatology Mexican Board and granted another scholarship for Hospital Ramo´n y Cajal, in
Madrid,Spain.HewentbacktoMexicoandin1983joined thestaffofrheumatologistsattheHospitalde
EspecialidadesCentroMedicoLaRaza,Mexico.From1990to1992hewastrainedasaresearchfellowin
RheumatologyattheUniversityofSouthFlorida,andtheLouisianaStateUniversity(LSU).From1992till
datehebelongstotheMexicanNationalSystemofInvestigators.In2004hewasappointedastheHeadof
Research Division. He is currently the Director of Education and Research, Hospital de Especialidades
‘‘Antonio Fraga Mouret’’ del Centro Me´dico Nacional La Raza.
Dr. Jara is a professor of rheumatology at the Universidad Nacional Auto´noma de Me´xico. He was
PresidentoftheMexicanCollegeofRheumatologyfrom2000to2001,andPresidentoftheMexicanBoard
of Rheumatology from 2001 to 2002.
Dr. Jara has written many scientific papers, reviews, and book chapters on different subjects, especially
ontheroleofhormonesinsystemiclupuserythematosus(SLE)andotheraututoimmunnediseasesbutalso
on pregnancy in SLE and antiphospholipid syndrome, and on accelerated atherosclerosis in autoimmune
diseases. He is married and has three children.
ix
List of Contributors
Vero´nica Abad Paul E. Belchetz
Hospital Pablo Tobon Uribe, Medellı´n, Colombia ConsultantPhysician/Endocrinologist,Department
ofEndocrinology,LeedsGeneralInfirmary,Great
Mauricio S. Abrao George Street, Leeds LS1 3EX UK
Gynecology Department, Medical School, Univer-
sity of Sa˜o Paulo, Sa˜o Paulo, Brazil Antonio Bellastella
Department of Clinical and Experimental Medi-
Ramzi Ajjan cine and Surgery ‘‘F. Magrassi, A. Lanzara’’,
Senior Lecturer in Diabetes and Endocrinology, Second University of Naples, Napoli, Italy
Academic Unit of Molecular Vascular Medicine,
LIGHT Laboratories, Clarendon Way, The Corrado Betterle
University of Leeds, Leeds, UK Chair of Clinical Immunology and Allergy,
Department of Medical and Surgical Sciences,
Howard Amital EndocrineUnit,UniversityofPadua,ViaOspedale
DepartmentofMedicine‘D’,MeirMedicalCenter, Civile 105, I-35128, Padua, Italy
Kfar-Saba, Tel-Aviv University, Tel-Aviv, Israel
Johannes W.J. Bijlsma
Juan-Manuel Anaya DepartmentofRheumatologyandClinicalImmu-
Corporacio´n para Investigaciones Biologicas, nology, University Medical Center Utrecht, Box
Cra, 72A No. 78B-141, Universidad del Rosario, 85500 3508 GA, Utrecht, The Netherlands
Medellı´n, Colombia
Antonio Bizzarro
Yoav Arnson Department of Clinical and Experimental Medi-
Department of Medicine ‘D’, Meir Medical cine and Surgery ‘‘F. Magrassi, A. Lanzara’’,
Center,Kfar-Saba,Tel-AvivUniversity, Tel-Aviv, Second University of Naples, Napoli, Italy
Israel
Ricardo Blanco
Fabiola Atzeni Rheumatology Division, Hospital Universitario,
Laboratory of Experimental Rheumatology and Marques de Valdecilla, Santander, Spain
Neuroendocrino-Immunology, Department of
Internal Medicine I, University Hospital, 93042 Francisco Blanco-Favela
Regensburg, Germany; Rheumatology Unit, Chief of Immunology Research Unit, Hospital de
University Hospital L. Sacco, Milan, Italy Pediatria, Centro Medico Nacional Siglo XXI,
IMSS, Mexico City, Mexico
Jennifer M. Barker
Barbara Davis Center for Childhood Diabetes, Eloisa Bonfa
UniversityofColoradoatDenverHealthSciences DisciplinadeReumatologia,FaculdadedeMedicina
Center, 1775 N. Ursula Street, PO Box 6511, daUniversidadedeSa˜oPaulo,Av.Dr.Arnaldo455,
A140, Aurora, CO 80045-6511, USA 31 andar, Sa˜o Paulo (SP), CEP- 01246-903, Brazil
xi
xii ListofContributors
Lı´dice Brada˜o Tavares Rodrigo Corena
DepartmentofMolecularandClinicalEndocrino- Cellular Biology and Immunogenetics Unit,
logy and Oncology, Section of Endocrinology, Corporacio´nparaInvestigacionesBiolo´gicas,Cra,
University ‘‘Federico II’’, via S. Pansini 5, 80131 72A No. 78B-141, Medellı´n, Colombia
Naples, Italy; Department of Endocrinology and
Metabolism, Hospital Brigadeiro, Av. Brigadeiro Sara Cortes
Luis Antonio, 2651, Sa˜o Paulo 01401-901, SP, Specialist Registrar in Rheumatology, Portuguese
Brazil Institute of Rheumatology, R. Beneficieˆncia, 7,
1050-034, Lisboa, Portugal
Pilar Brito-Zeron
Department of Autoimmune Diseases, IDIBAPS, Maurizio Cutolo
Hospital Clinic, Barcelona, Spain Research Laboratory and Division of Rheumato-
logy,DepartmentofInternalMedicine,Universityof
Frank Buttgereit Genova,VaileBenedettoXV,6,16132Genova,Italy
Department of Rheumatology and Clinical Immu-
nology,Charite´ UniversityHospital,Chariteplatz1, Jose´ Antonio P. da Silva
10117 Berlin, Germany Department of Rheumatology, Hospitais da
Universidade de Coimbra, Portugal
Silvia Capellino
Laboratory of Experimental Rheumatology and Annamaria De Bellis
Neuroendocrino-Immunology, Department of Department of Clinical and Experimental Medi-
Internal Medicine I, University Hospital, 93042 cine and Surgery ‘‘F. Magrassi, A. Lanzara’’,
Regensburg, Germany Second University of Naples, Napoli, Italy
Roberto Caporali Gerard Espinosa
Cattedra di Reumatologia, Universita´ di Pavia, Department of Autoimmune Diseases, IDIBAPS,
UO Reumatologia Poloclinico S. Matteo, IRCCS Hospital Clinic, Barcelona, Spain
Policlinico S.Matteo Foundation, Piazzale Golgi
2, 27100 Pavia, Italy Luis R. Espinoza
Rheumatology Section, School of Medicine,
Howard J.A. Carp LouisianaStateUniversity,NewOrleans,Louisiana,
Department of Obstetrics and Gynecology, Sheba USA
Medical Center, Tel Hashomer, Israel
Diego Ferone
Ricard Cervera Department of Endocrine and Medical Sciences
Department of Autoimmune Diseases, IDIBAPS, andCenterofExcellenceforBiomedicalResearch,
Hospital Clinic, Barcelona, Spain University of Genova, Viale Benedetto XV, 6,
16132, Genova, Italy
Carol E. Chu
Consultant Clinical Geneticist, Department of Miguel A. Gonzalez-Gay
Clinical Genetics, St. James’s Hospital, Beckett Division of Rheumatology, Hospital Xeral-Calde,
St., Leeds LS9 7TF, UK c/Dr. Ochoa s/n, 27004 Lugo, Spain
Annamaria Colao David Isenberg
DepartmentofMolecularandClinicalEndocrino- Centre for Rheumatology Research, UCL Divi-
logy and Oncology, Section of Endocrinology, sion of Medicine, Room 331 3rd Floor, The
University ‘‘Federico II’’, via S. Pansini 5, 80131 Windeyer Building, 46 Cleveland Street, London
Naples, Italy W1T 4JF, United Kingdom
ListofContributors xiii
Luis J. Jara Sandra G. Pasoto
DirectionofEducationandResearch,Hospitalde Disciplina de Reumatologia, Faculdade de Medi-
Especialidades, Centro Medico La Raza, IMSS, cinadaUniversidadedeSa˜oPaulo,Av.Dr.Arnaldo
Universidad Nacional Auto´noma de Me´xico, 455, 31 andar, Sa˜o Paulo (SP), CEP-01246-903,
Seris/Zaachila S/N, Colonia La Raza, C.P. Brazil
02990, Mexico City, Mexico
Elena Peeva
Ana Jero´nimo Department of Microbiology and Immunology,
Specialist Registrar in Internal Medicine, Pedro Albert Einstein College of Medicine, Bronx, NY,
Hispano Hospital, Matosinhos, Portugal USA
Munther Khamashta
Michelle Petri
LupusResearchUnit,TheRayneInstitute,Guy’s,
John Hopkins University School of Medicine,
King’s and St. Thomas’ School of Medicine,
1830 E. Monument Street, Suite 7500, Baltimore,
St. Thomas’ Hospital, Lambeth Palace Road,
MD, USA
London, SE1 7EH, UK
Rosario Pivonello
Gaetano Lombardi
Department of Molecular and Clinical Endocri-
Department of Molecular and Clinical Endocrino-
nology and Oncology, Section of Endocrinology,
logy and Oncology, Section of Endocrinology,
University ‘‘Federico II’’, via S. Pansini 5, 80131
University ‘‘Federico II’’, via S. Pansini 5, 80131
Naples, Italy
Naples, Italy
Sergio Podgaec
Mario Garcı´a-Carrasco
Gynecology Department, Medical School, Uni-
Beneme´rita Universidad Auto´noma de Puebla,
versity of Sa˜o Paulo, Sa˜o Paulo, Brazil
Me´xico
Fabio Presotto
Gabriela Medina
Department of Medical and Surgical Sciences,
Associated Investigator, Clinical and Epidemio-
University of Padua, and Unit of Internal Medi-
logy Research Unit, Hospital de Especialidades,
cine, General Hospital of Este (Padua), Via San
Centro Medico La Raza, IMSS, Mexico City,
Fermo 10 I-35042 Este, Italy
Mexico
Carlomaurizio Montecucco Manuel Ramos-Casals
Cattedra di Reumatologia, Universita´ di Pavia, Department of Autoimmune Diseases, IDIBAPS,
Hospital Clinic, Barcelona, Spain
UO Reumatologia Poloclinico S. Matteo, IRCCS
Policlinico S. Matteo Foundation, Piazzale Golgi
2, 27100 Pavia, Italy Alejandro Ruiz-Argu¨elles
Laboratorios Clı´nicos de Puebla, Me´xico
Carmen Navarro
Subdirector of Clinical Research, Instituto Miguel A. Saavedra
Nacional de Enfermedades Respiratorias, SSA, Department of Rheumatology, Hospital de
Mexico Especialidades, Centro Me´dico La Raza, IMSS,
Mexico City, Mexico
Asher Ornoy
Teratology Laboratory, Department of Anatomy Piercarlo Sarzi-Puttini
and Cell Biology, Hebrew University, Hadassah RheumatologyUnit,UniversityHospitalL.Sacco,
Medical School, Jerusalem Milan, Italy
xiv ListofContributors
Gabriela Schiechl Sangeeta D. Sule
Laboratory of Experimental Rheumatology and John HopkinsUniversity Schoolof Medicine, 200
Neuroendocrino-Immunology, Department of N. Wolfe Street, Suite 2126, Baltimore, MD 2105,
Internal Medicine I, University Hospital, 93042 USA
Regensburg, Germany
Yaron Tomer
R. Hal Scofield Division of Endocrinology, The Vontz Center
Arthritis and Immunology Program, Oklahoma for Molecular Studies, University of Cincinnati,
Medical Research Foundation; Endocrinology Cincinnati VA Medical Center, 3125 Eden
and Diabetes Section, Department of Medicine, Avenue, Cincinnati, OH 45267, USA
University of Oklahoma Health Sciences Center;
Department of Veterans Affairs Medical Center,
Christian Toso
Oklahoma City, OK, USA
Department of Surgery, University of Alberta,
Edmonton, Alberta, Canada
A.M. James Shapiro
Department of Surgery, University of Alberta,
Imad Uthman
Edmonton, Alberta, Canada
Division of Rheumatology, Faculty of Medicine,
American University of Beirut, Medical Center,
Yehuda Shoenfeld
P.O. Box 113-6044, Beirut, Lebanon
Department of Medicine ‘B’ and Center for
Autoimmune Diseases, Sheba Medical Center,
Tel-Hashomer 52621, Israel; Incumbent of the Sara E. Walker
Department of Internal Medicine, Division of
Laura Schwarz-Kipp Chair for Research of Auto-
Immunology and Rheumatology, University of
immune Diseases, Tel-Aviv University, Tel-Aviv,
Israel Missouri-Columbia, MA427, One Hospital Drive
DC043.00, Columbia, MO 65212, USA
Rainer H. Straub
Laboratory of Experimental Rheumatology and Gisele Zandman-Goddard
Neuroendocrino-Immunology, Department of Department of Medicine, Wolfson Medical Cen-
Internal Medicine I, University Hospital, 93042 ter, Holon, Israel; Sackler Faculty of Medicine,
Regensburg, Germany Tel Aviv University, Ramat Aviv, Israel
HandbookofSystemicAutoimmuneDiseases,Volume9
EndocrineManifestationsofSystemicAutoimmuneDiseases
SaraE.WalkerandLuisJ.Jara,editors
CHAPTER 1
Neuroendocrine Immune Control Mechanisms and
their Influence on Autoimmune Disease
(cid:2)
Silvia Capellino, Rainer H. Straub
Laboratory of Experimental Rheumatology and Neuroendocrino-Immunology,
Department of Internal Medicine I, University Hospital, Regensburg, Germany
1. Introduction but the reasons remained unclear for a long
time. Normally, stressful/inflammatory conditions
The first studies on rheumatoid arthritis (RA) activate the immune system and subsequently
focused on aspects of the immune system and the the hypothalamic–pituitary–adrenal (HPA) axis
role of tissue-destructive mesenchymal cells such through peripheral and central production of
as fibroblasts and osteoclasts and their factors inflammatory cytokines. Nowadays we know that
(Mu¨ller-Ladneretal.,1996;Bla¨Xetal.,1999;Walsh patients with RA have plasma cortisol levels
and Gravallese, 2004). Since the beginning of the similar to control subjects even in the presence of
1980s,ithasbecame evidentthatpatientswithRA high amounts of circulating inflammatory cyto-
showedmultiplealterationsoftheendocrinesystem kines (see below) (Crofford et al., 1997). It is
and the peripheral and even the central nervous obvious that there is a deficit in cortisol secre-
system (CNS), and different studies demonstrated tion relative to inflammation (see 2.2.). After
that the nervous system can directly alter the experimentally induced physical or psycholo-
immune response (Levine et al., 1985). In order to gical stress, RA patients present inappropriately
understand the pathophysiology of RA, it is low cortisol levels because of defects in neuroen-
necessarytoconsiderthesedifferentalterationsand docrine axes. For example, as a consequence
how they interact with each other. In this review, of physical exercise, inducing changes in corti-
alterations of the endocrine and nervous systems sol release comparable to psychological stress,
and new therapeutic strategies are discussed. serum levels of cortisol decreased in patients
with RA but increased in healthy controls
(Fig. 1) (Pool et al., 2004). These results reveal
2. Systemic neuroendocrine alterations that stress in combination with a deficient HPA
axis activity leads to an unexpected decrease in
2.1. Decreased responsiveness of the HPA cortisol. On the contrary, the stress of insulin-
axis to stressful events induced hypoglycemia leads to a normal corti-
sol increase in patients with RA (Rovensky
et al., 2002). Therefore, we hypothesize that
It is well known that stressful events can
in RA patients, mild psychological or physical
change the activity of RA (Zautra et al., 1997),
stress leads to activation of the immune system,
whereas strong, acute stress (hypoglycemia) can
(cid:2)
Correspondingauthor.
have immunosuppressive effects (Straub et al.,
Tel.:[phone];Fax:[phone]
2005).
E-mailaddress:[email protected]
r2008PublishedbyElsevierB.V.
DOI:10.1016/S1571-5078(07)00201-2