Autoimmunity Reviews 4 (2005) 130 – 136

www.elsevier.com/locate/autrev

Epidemiology of adult rheumatoid arthritis

Yannis Alamanosa, Alexandros A. Drososb,*
a
Department of Hygiene and Epidemiology, Medical School, University of Ioannina, Ioannina, Greece
b
Rheumatology Clinic, Department of Internal Medicine, Medical School, University of Ioannina, 45110 Ioannina, Greece
Received 1 September 2004; accepted 5 September 2004
Available online 19 October 2004

Abstract

Several incidence and prevalence studies of rheumatoid arthritis (RA) have been reported during the last decades,
suggesting a considerable variation of the disease occurrence among different populations. The majority of studies curried
out in Northern European and North American areas estimate a prevalence of 0.5–1%, and a mean annual incidence of 0.02–
0.05%. The occurrence of the disease seems to be lower in other parts of the world. Some studies from North American,
North European, and Japanese populations suggest a decline in both the prevalence and incidence of the disease after the
1960s. RA is related to an increased mortality, and the expected survival of RA patients is likely to decrease 3–10 years.
There is epidemiological evidence that genetic factors are related to an increased risk of RA. However, RA is considered to
be a multifactorial disease, resulting from the interaction of both genetic and environmental factors, which contribute to its
occurrence and expression. The main risk factors for the disease include genetic susceptibility, sex and age, smoking,
infectious agents, hormonal, dietary, socioeconomic, and ethnic factors. Most of these factors are likely to be associated with
both disease occurrence and severity.
D 2004 Elsevier B.V. All rights reserved.

Keywords: Rheumatoid arthritis; Epidemiology; Shared epitope; Incidence; Prevalence

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131
2. Descriptive epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131
2.1. Geographic variation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131
2.2. Time trends . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132
2.3. Mortality and survival . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132
3. Risk factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132

* Corresponding author. Tel.: +30 26510 99755/97503; fax: +30 26510 97054/97016.
E-mail address: adrosos@cc.uoi.gr (A.A. Drosos).

1568-9972/$ - see front matter D 2004 Elsevier B.V. All rights reserved.
doi:10.1016/j.autrev.2004.09.002
 Y. Alamanos, A.A. Drosos / Autoimmunity Reviews 4 (2005) 130–136 131

3.1. Genetic factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132

3.2. Age and gender . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133
3.3. Smoking . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133
3.4. Socioeconomic factors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133
3.5. Infectious agents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133
3.6. Hormonal factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134
3.7. Dietary factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134
3.8. Ethnicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134
4. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 134
Take-home messages. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135

1. Introduction may have included cases that do not correspond to the

The study of the epidemiological profile of a
specific disease includes its frequency, severity, and
distribution among different populations and human
groups (descriptive epidemiology), as well as the
influence of genetic and environmental factors on the
occurrence and variation of the disease (analytical
epidemiology risk factors). The study of the associ-
ation of the disease with some personal character-
istics, such as age, gender, racial or social group, and
others is in the limit between descriptive and
analytical epidemiology. In this review, we consider
those factors as potential risk factors for rheumatoid
arthritis (RA).
2. Descriptive epidemiology
RA is a chronic inflammatory disease affecting the
synovium, leading to joint damage and bone destruc-
tion and causes severe disability and increases mortal-
ity [1]. Several incidence and prevalence studies of
RA have been reported during the last decades,
suggesting a considerable variation of the disease
occurrence among different populations. However, the
studies published on RA epidemiology present meth-
odological differences. These differences include the
methods of case identification and case recording, as
well as the type of incidence and prevalence rates. The
1987 revised American College of Rheumatology
criteria are the currently accepted criteria for RA
diagnosis and classification. These criteria replaced
the earlier existing criteria (1958, New York classi-
fication criteria). As a consequence, earlier studies
current definition of RA. In addition, the methods of
case ascertainment differ among studies. These and
other methodological differences put some limitations
in the comparison of descriptive studies and the
interpretation of different findings. However, it is
likely that the epidemiology of RA presents some
characteristic trends, which could be considered as
independent from methodological issues [2,3].
2.1. Geographic variation
Several prevalence and incidence studies of RA
have been reported during the last decades, suggesting
a considerable variation of the disease occurrence
among different populations. The majority of preva-
lence studies curried out in Northern European and
North American areas estimate a prevalence of 0.5–
1.1% [2–9]. Studies from Southern European countries
report a prevalence of 0.3–0.7% [10–15]. Studies from
developing countries also report a relatively lower
prevalence of the disease (between 0.1% and 0.5%)
[3,16–22]. A higher prevalence has been reported in
certain Native Americans, and a very low frequency of
RA in some areas of rural Africa [3,23].
The annual incidence rates of RA vary between 20
and 50 cases per 100,000 inhabitants in North
American and North European countries [4,5,9,24–
26]. There are only few studies from Southern
European countries indicating a relatively lower
occurrence of the disease [10,27]. There are no studies
on RA incidence from developing countries. Previous
studies from Japan suggested a relatively higher
incidence of the disease, but all of them were based
on previous identification criteria, and recent data do
132 Y. Alamanos, A.A. Drosos / Autoimmunity Reviews 4 (2005) 130–136

not confirm this picture [28]. Table 1 summarizes data
on RA prevalence and incidence for several areas of
the world and several countries.
2.2. Time trends
There are relatively limited data on trends in the
incidence and prevalence of RA over time. Some
studies from North American, North European, and
Japanese populations suggest a decline in both the pre-
valence and the incidence of the disease after the 1960s.
However, this trend could be related to methodological
issues of the epidemiological studies, which were
mentioned above. Differences in case ascertainment,
case identification, and access to health care could
partly explain the decline observed [9,25,28].
2.3. Mortality and survival
Mortality rates are higher among RA patients than
in the general population. The mortality rates reported
vary widely among studies. They are higher in
hospital-based studies and relatively lower (but still
higher than in the general population) in population-
based studies. The expected survival of RA patients is
likely to decrease 3–10 years according to the severity
of the disease and the age of disease onset. The causes
of death do not differ significantly among RA patients
and the general population they come from. It can be
said that the majority of affected individuals die from
the same causes as the general population, but at a
younger age [2,9,25,29,30].

3. Risk factors
Table 1
Prevalence and incidence rates of RA worldwide (cases per 100
A risk factor is any factor (genetic, environmental,
inhabitants)
or personal) that increases the risk of developing a
Population Prevalence Incidence
rates rates
disease. There is a general consensus that RA is a
multifactorial disease, resulting from the interaction of
North America ! USA 0.9–1.1 0.02–0.07
(general population)
both genetic and environmental factors, which con-
! USA 5.3–6.0 0.09–0.89 tribute to its occurrence and expression.
(native-Americans) Several environmental factors have been suspected
North Europe ! England 0.8–1.10 0.02–0.04 and studied as possibly related to an increased risk of
! Finland 0.8 0.03–0.04 RA, as well as to a worse or improved prognosis of the
! Sweden 0.5–0.9
! Norway 0.4–0.5 0.02–0.03
disease. However, the impact of most of these factors
! Netherlands 0.9 0.05 on the risk of developing RA and the expression of the
! Denmark 0.9 disease remains still uncertain. On the other hand,
! Ireland 0.5 there is an epidemiologic evidence that genetic factors
South Europe ! Spain 0.5 are related to an increased risk of RA. The nature and
! France 0.6 0.01
! Italy 0.3
the impact of this genetic risk is becoming clearer
! Greece 0.3–0.7 0.02 during the last years. We describe here the most
! Yugoslavia 0.2 important personal, lifestyle, environmental, and
South America ! Argentina 0.2 genetic factors that have been proposed and studied
! Brazil 0.5 as influencing the occurrence of the disease. Some of
! Colombia 0.1
Asia ! Japan 0.3 0.04–0.09
these factors have also been studied as possibly
! China 0.2–0.3 associated with the course and the severity of RA.
! Taiwan 0.3
! Indonesia 0.2–0.3 3.1. Genetic factors
! Philippines 0.2
! Pakistan 0.1
Middle East ! Egypt 0.2
There is evidence that the occurrence and the
! Israel 0.3 severity of RA are related to genetic factors. Twin
! Oman 0.4 and family studies offered a strong suggestion that the
! Turkey 0.5 risk of the disease among relatives of affected
Africa 0–0.3 individuals is influenced by shared genetic factors.
 Y. Alamanos, A.A. Drosos / Autoimmunity Reviews 4 (2005) 130–136
Studies carried out in Caucasian patients with estab-
lished and advanced disease indicated an association
of RA with alleles encoding a bshared epitopeQ (called
brheumatoid epitopeQ). These studies also suggested a
significant association of brheumatoid epitopeQ with
disease severity and outcome [31]. The role of other
genes has also been studied and several associations
have been described. Some studies indicate an
association between certain tumor necrosis factor
alpha alleles and RA occurrence and severity, but
others failed to confirm those associations. A number
of DR specificities have been reported to be protective
factors of RA. Interactions between genes in the
etiology of RA have also been proposed.
For the moment, it is not clear whether genetic
factors are related to the risk of RA or to the severity
of the disease or both of them. Although the available
data do not clarify completely the role of genetic
factors in disease susceptibility and severity, their
impact on the epidemiology of RA is generally
accepted. The significant variations observed in the
incidence and prevalence of RA among different
populations or ethnic groups could partly been
explained by genetic variation in the HLA region,
and variation in the prevalence of bshared epitopeQ in
different populations [32,33].
3.2. Age and gender
The incidence of RA is higher in women than in
men. The sex ratio varies in most studies from about
2:1 to about 3:1. This difference suggests an influence
of reproductive and hormonal factors in the occur-
rence of the disease. However, the findings of several
studies give a conflicting picture on this issue. For the
moment, it is not clear how gender influences the
occurrence of RA [4,5,9].
The age of disease onset presents a peak in the fifth
decade of life according to the majority of epidemio-
logical studies. Some more recent studies suggest a
later onset of the disease [4,5,9,10,24–27].
3.3. Smoking
Smoking is likely to influence both the risk of
developing RA and the course of the disease. The
increased risk of RA associated with smoking has
been suggested in cross-sectional as well as in
133
longitudinal studies. The association appears to be
dose-dependent, and is most clear for heavy smokers.
The severity and outcome of RA appears also to be
influenced by smoking, although it is not clear which
clinical characteristics of the disease are related to
smoking. An increased risk for seropositive disease is
related to smoking habits [34,35].
3.4. Socioeconomic factors
Socioeconomic factors appear to influence the
course and the outcome of RA rather than the risk
of developing RA. Occupation, educational level,
marital status, and social group have been studied as
possible risk factors for disease susceptibility, or
predictors for disease severity and outcome. The
results of these studies are conflicting mainly as
concerning the impact of socioeconomic factors on
the risk of developing RA. However, the data
available suggest an association of adverse socio-
economic status with worse prognosis of the disease
[2,3].
3.5. Infectious agents
A potential involvement of infectious agents in
the occurrence of RA has been suggested and
studied for decades. It is possible that those agents
could trigger the development of the disease in a
genetically susceptible host. Several infectious agents
have been implicated in the etiology of the disease,
but there is not epidemiological evidence that those
agents could explain a considerable fraction of RA
cases [2,3].
Several potential associations of RA with infec-
tious agents have been suggested. They include
parvovirus, rubella virus, Epstein–Barr virus, borrelia
burgdorferi, and others. Increased titers of antibodies
among RA patients and clinical syndromes similar to
RA induced by some of these agents have been
reported. However, the role of infectious agents in the
occurrence of the disease remains unclear. Incident
cases of RA do not report a history of increased
number of infections, or any specific infections.
Furthermore, cases of RA do not present any time
or space clustering, which should be the case if there
was a direct association of RA development with
infections [2,3,36].
134 Y. Alamanos, A.A. Drosos / Autoimmunity Reviews 4 (2005) 130–136
3.6. Hormonal factors
The higher occurrence of RA in females than in
males suggests a possible role of hormonal factors in
disease susceptibility. Furthermore, estrogens are
known to have a stimulatory effect on the immune
system. Epidemiological studies tried to investigate
this association by studying the possible protective role
of pregnancy, the use of oral contraceptives and the
hormone replacement therapy after menopause [2,3].
Parity has been associated with reduced risk of de-
veloping RA. However, it is difficult to clarify whether
this association reflects any protective effect of
pregnancy or an increased risk for infertility before
the development of RA. There is also evidence that
pregnancy is associated with remission of the disease in
RA patients. This effect reverts in the post-partum
period.
The potential protective effect of the use of oral
contraceptives has been studied also. It seems that oral
contraceptives have a modulatory effect, protecting
mainly against severe disease rather than protecting
against RA occurrence. There are only few studies on
the effect of hormone replacement therapy, presenting
a conflicting picture [2,3,37].
3.7. Dietary factors
Several epidemiological studies suggest a potential
protective effect of lifelong consumption of fish, olive
oil, and cooked vegetables. The protective role of fish
consumption has been attributed to the effect of
omega-3 long chain polyunsaturated fatty acids
against poly-inflammatory disease. Mediterranean diet
as a whole has also been reported as a lifestyle factor
reducing the risk of developing RA, and protecting
against severe course of the disease. These observa-
tions could partly explain the geographical variations
of the disease occurrence, and severity [38,39].
3.8. Ethnicity
Differences in the occurrence and the clinical
expression of RA among different populations have
been reported by several studies. The significant
geographic variations of the disease occurrence, and
the increased incidence observed in some specific
ethnic groups, suggest an association of RA with
ethnicity [2,3]. The differences observed may reside in
the different distribution of environmental and genetic
factors, as well as in their interaction. Lifestyle factors
possibly associated with the risk and the severity of
RA (such as dietary factors) may differ significantly
among ethnic groups. The prevalence of rheumatoid
epitope is likely to present important variations in
different racial groups. In addition, the association of
rheumatoid epitope with the development of erosive
disease seems to present significant differences among
ethnic groups. These observations indicate that
ethnicity could be considered as an independent risk
factor, reflecting interactions between several genetic
and environmental factors [2,3,32,40].
4. Conclusions
Significant variations of RA incidence and preva-
lence have been observed among different popula-
tions. It seems that there is a relative decrease in the
disease occurrence during the last decades. There is a
general consensus that RA is a multifactorial disease,
resulting from the interaction of both genetic and
environmental factors, which contribute to its occur-
rence and expression (Fig. 1). Several risk factors for
RA have been suggested. They include genetic
susceptibility, sex, age, ethnicity, socioeconomic
characteristics, smoking, diet, infectious agents, and
Fig. 1. Hypothetical model of rheumatoid arthritis causation:
interaction of genes with environmental factors, as well as with
hormonal and lifestyle factors over time in an individual, may give
rise to disease evolution and its expression.
 Y. Alamanos, A.A. Drosos / Autoimmunity Reviews 4 (2005) 130–136
hormonal factors. RA is associated with significantly
increased mortality.
Take-home messages
! Incidence and prevalence studies of RA suggest a
considerable variation of the disease occurrence
among different populations.
! RA is a multifactorial disease, resulting from the
interaction of both genetic and environmental
factors.
! The main factors associated with RA occurrence
and expression include genetic susceptibility, as
well as several environmental, lifestyle, and
personal characteristics.
! The expected survival of RA patients is likely to
decrease 3–10 years according to the severity of
the disease and the age of disease onset.
References
[1] Choy EH, Panayi GS. Cytokine pathways and joint inflamma-
tion in rheumatoid arthritis. N Engl J Med 2001;344:907 – 16.
[2] MacGregor AJ, Silman AJ. Rheumatoid arthritis and other
synovial disorders: classification and epidemiology. In: Hoch-
berg MC, Silman AJ, Smolen JS, Weinblatt ME, Weisman
MH, editors. Rheumatology, 3rd ed. Mosby. p. 757 – 63.
[3] Silman AJ, Hochberg MC. Epidemiology of the rheumatic
diseases. 2nd edition. Oxford University Press.
[4] Riise T, Jacobsen BK, Gran JT. Incidence and prevalence of
rheumatoid arthritis in the county of Troms, northern Norway.
J Rheumatol 2001;27:1386 – 9.
[5] Gabriel SE, Crowson CS, O’Fallon WM. The epidemiology of
rheumatoid arthritis in Rochester, Minnesota, 1955–1985.
Arthritis Rheum 1999;42:415 – 20.
[6] Simonsson M, Bergman S, Jacobsson LT, Petersson IF,
Svensson B. The prevalence of rheumatoid arthritis in
Sweden. Scand J Rheumatol 1999;28:340 – 3.
[7] Symmons D, Turner G, Webb R, Asten P, Barrett E, Lunt M
et al. The prevalence of rheumatoid arthritis in the United
Kingdom: new estimates for a new century. Rheumatology
2002;41:793 – 800.
[8] Power D, Codd M, Ivers L, Sant S, Barry M. Prevalence of
rheumatoid arthritis in Dublin, Ireland: a population based
survey. Ir J Med Sci 1999;168:197 – 200.
[9] Aho K, Kaipiainen-Seppanen O, Heliovaara M, Klaukka T.
Epidemiology of rheumatoid arthritis in Finland. Semin
Arthritis Rheum 1998;27:325 – 34.
[10] Drosos AA, Alamanos I, Voulgari PV, Psychos DN,
Katsaraki A, Papadopoulos I, et al. Epidemiology of adult
135
rheumatoid arthritis in northwest Greece 1987–1995. J
Rheumatol 1997;24:2129 – 33.
[11] Andrianakos A, Trontzas P, Christoyannis F, Dantis P,
Voudouris C, Georgountzos A, et al. Prevalence of rheumatic
diseases in Greece: a cross-sectional population based
epidemiological study. The ESORDIG Study. J Rheumatol
2003;30:1589 – 601.
[12] Carmona L, Villaverde V, Hernandez-Garcia C, Ballina J,
Gabriel R, Laffon A. The prevalence of rheumatoid arthritis
in the general population of Spain. Rheumatology 2002;41:
88 – 95.
[13] Cimmino MA, Parisi M, Moggiana G, Mela GS, Accardo S.
Prevalence of rheumatoid arthritis in Italy: the Chiavari Study.
Ann Rheum Dis 1998;57:315 – 8.
[14] Saraux A, Guedes C, Allain J, Devauchelle V, Valls I,
Lamour A, et al. Prevalence of rheumatoid arthritis and
spondyloarthropathy in Brittany, France. Societe de Rheuma-
tologie de l’Ouest. J Rheumatol 1999;26:2622 – 7.
[15] Stojanovic R, Vlachinac H, Palic-Obradovic D, Janosevic S,
Adanja B. Prevalence of rheumatoid arthritis in Belgrade,
Yugoslavia. Br J Rheumatol 1998;37:729 – 32.
[16] Spindler A, Bellomio V, Berman A, Lucero E, Baigorria M,
Paz S, et al. Prevalence of rheumatoid arthritis in Tucuman,
Argentina. J Rheumatol 2002;29:1166 – 70.
[17] Pountain G. The prevalence of rheumatoid arthritis in the
Sultanate of Oman. Br J Rheumatol 1991;30:24 – 8.
[18] Akar S, Birlik M, Gurler O, Sari I, Onen F, Manisali M
et al. The prevalence of rheumatoid arthritis in an urban
population of Izmir-Turkey. Clin Exp Rheumatol 2004;22:
416 – 20.
[19] Darmawan J, Muirden KD, Valkenburg HA, Wigley RD. The
epidemiology of rheumatoid arthritis in Indonesia. Br J
Rheumatol 1993;32:537 – 40.
[20] Lau E, Symmons D, Bankhead C, MacGregor A, Donnan S,
Silman A. Low prevalence of rheumatoid arthritis in the urba-
nized Chinese of Hong Kong. J Rheumatol 1993;20:1133 – 7.
[21] Dai SM, Han XH, Zhao DB, Shi YQ, Liu Y, Meng JM.
Prevalence of rheumatic symptoms, rheumatoid arthritis,
ankylosing spondylitis, and gout in Shanghai, China: a
COPCORD study. J Rheumatol 2003;30:2245 – 51.
[22] Senna ER, De Barros AL, Silva EO, Costa IF, Pereira LV,
Ciconelli RM, et al. Prevalence of rheumatic diseases in
Brazil: a study using the COPCORD approach. J Rheumatol
2004;31:594 – 7.
[23] Silman AJ, Ollier W, Holligan S, Birrell F, Adebajo A, Asuzu
MC, et al. Absence of rheumatoid arthritis in a rural Nigerian
population. J Rheumatol 1993;20:618 – 22.
[24] Symmons DP, Barrett EM, Bankhead CR, Scott DG, Silman
AJ. The incidence of rheumatoid arthritis in the United
Kingdom: results of the Norfolk Arthritis Register. Br J
Rheumatol 1994;33:735 – 9.
[25] Doran MF, Pond GR, Crowson CS, O’Fallon WM, Gabriel
SE. Trends in incidence and mortality in rheumatoid arthritis
in Rochester, Minnesota, over a forty-year period. Arthritis
Rheum 2002;46:625 – 31.
[26] Soderlin MK, Borjesson O, Kautiainen H, Skogh T, Leirisalo-
Repo M. Annual incidence of inflammatory joint diseases in a
136 Y. Alamanos, A.A. Drosos / Autoimmunity Reviews 4 (2005) 130–136

population study in southern Sweden. Ann Rheum Dis
2002;61:911 – 5.
[27] Guillemin F, Briancon S, Klein JM, Sauleau E, Pourel J. Low
incidence of rheumatoid arthritis in France. Scand J Rheumatol
1994;23:264 – 8.
[28] Shichikawa K, Inoue K, Hirota S, Maeda A, Ota H, Kimura
M, et al. Changes in the incidence and prevalence of
rheumatoid arthritis in Kamitonda, Wakayama, Japan,
1965–1996. Ann Rheum Dis 1999;58:751 – 6.
[29] Wolfe F, Mitchell DM, Sibley JT, Fries JF, Bloch DA,
Williams CA, et al. The mortality of rheumatoid arthritis.
Arthritis Rheum 1994;37:481 – 94.
[30] Gabriel SE, Crowson CS, Kremers HM, Doran MF,
Turesson C, O’Fallon WM, et al. Survival in rheumatoid
arthritis: a population-based analysis of trends over 40 years.
Arthritis Rheum 2003;48:54 – 8.
[31] Weyand CM, Hicok KC, Conn DL, Goronzy JJ. The influence
of HLA-DRB1 genes on disease severity in rheumatoid
arthritis. Ann Intern Med 1992;117:801 – 6.
[32] Gorman JD, Lum RF, Chen JJ, Suarez-Almazor ME, Thomson
LA, Criswell LA. Impact of shared epitope genotype and
ethnicity on erosive disease: a meta-analysis of 3,240 rheuma-
toid arthritis patients. Arthritis Rheum 2004;50:400 – 12.
[33] Ioannidis JP, Tarassi K, Papadopoulos IA, Voulgari PV,
Boki KA, Papasteriades CA, et al. Shared epitopes and
rheumatoid arthritis: disease associations in Greece and
meta-analysis of Mediterranean European populations.
Semin Arthritis Rheum 2002;31:361 – 70.
[34] Wilson K, Goldsmith CH. Does smoking cause rheumatoid
arthritis? J Rheumatol 1999;26:1 – 3.
[35] Harrison BJ. Influence of cigarette smoking on disease outcome
in rheumatoid arthritis. Curr Opin Rheumatol 2002;14:93 – 7.
[36] Silman A, Bankhead C, Rowlingson B, Brennan P, Sym-
mons D, Gatrell A. Do new cases of rheumatoid arthritis
cluster in time or in space? Int J Epidemiol 1997;26:628 – 34.
[37] Buyon JP. The effects of pregnancy on autoimmune diseases. J
Leukoc Biol 1998;63:281 – 7.
[38] Skoldstam L, Hagfors L, Johansson G. An experimental study
of a Mediterranean diet intervention for patients with
rheumatoid arthritis. Ann Rheum Dis 2003;62:208 – 14.
[39] Cleland LG, James MJ, Proudman SM. The role of fish oils in
the treatment of rheumatoid arthritis. Drugs 2003;63:845 – 53.
[40] Drosos AA, Lanchbury JS, Panayi GS, Moutsopoulos HM.
Rheumatoid arthritis in Greek and British patients. A
comparative clinical, radiologic, and serologic study. Arthritis
Rheum 1992;35:745 – 8.

Corticosteroid administration and dendritic cells in ITP

Immune thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by low platelet count
resulting from antibody-mediated destruction of platelets. The production of these IgG anti-platelet
autoantibodies is drived by T-lymphocytes which can be activated by antigen-presenting cells such as
dendritic cells. Hsu et al. (Platelets 2004;15:451) measured dendritic cell population in peripheral blood of
three ITP patients before and after the administration of prednisone. Both counts of myeloid and lymphoid
dendritic cells in the blood of ITP patients were greatly reduced after the administration of prednisone.
The decrease in circulating dendritic cells was associated with an increase of platelets counts. The authors
postulated that corticosteroid therapy may decrease the effects of the autoantibody on platelets in ITP
patients by reduce the number of circulating dendritic cells.

Central tolerance induced by mature T cells

Induction of immunological tolerance is desirable for the treatment and prevention of autoimmunity. Tian
et al. (J Immunol 2004;173:7217) report that adoptive transfer of MHC class I disparate mature T cells at
the time of reconstitution of mice with syngeneic bone marrow resulted in specific tolerance to allogeneic
skin grafts that were matched to the T cell donor strain. These mature allogeneic T cells survived long-
term in reconstituted hosts and re-entered the thymus. Using transgenic mice expressing an alloantigen-
reactive TCR the authors revealed that expression of allogeneic MHC class I on adoptively transferred
mature T cells mediated negative selection of developing alloreactive T cells in the thymus. The authors
concluded that mature allogeneic T cells were able to mediate central deletion of alloreactive cells and
induced transplantation tolerance.