LE MALATTIE REUMATICHE AUTOIMMUNI: PERCHE' DONNA? PERCHE' NON UOMO? NUOVE TERAPIE PER NUOVI ORIZZONTI - martedì 8 ottobre, ore 10 - Associazione ...
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martedì 8 ottobre, ore 10 LE MALATTIE REUMATICHE AUTOIMMUNI: PERCHE’ DONNA? PERCHE’ NON UOMO? NUOVE TERAPIE PER NUOVI ORIZZONTI Renato Carignola, immunologo Claudia Lomater, reumatologo
Il dismorfismo sessuale Tamara de Lempicka - 1932
Venere di Milo, 130 A.C.
G Klimt - Medicina - 1901
La medicina ha ignorato per lungo tempo la differenza fra uomini e donne: • che si ammalano in modo diverso, • presentano gravità di sintomi e decorso diversi per la stessa patologia, • hanno risposte diverse rispetto all’assunzione di farmaci, • hanno diversa sopravvivenza alla stessa patologia.
Il sistema immunitario e il sesso L’incidenza di influenza stagionale è più alta negli uomini che nelle donne il rischio di morte per tumore è di 1.6 volte maggiore negli uomini che nelle donne
www.driverlayer.com
Let's start from the beginning
…ma…
…quando le cellule del sistema
immunitario sono esposte a virus, batteri,
parassiti, allergeni, tossine o antigeni
«self»…
la risposta immunitaria di una donna
differisce da quella di un uomo!
Women
- enhanced antibody production
- increased cell-mediated
responses following immunization
- higher CD4+ T cell counts
- increased CD4/CD8 ratio
- Higher levels of plasma IgM
- greater Th1 cytokine production
Men:
- produce a more intense
inflammatory response to
infectious organisms
The significance of these changes remain poorly defined since
there does not appear to be significant differences in susceptibility
to infection or inflammation degrees between sexes«Nelle malattie reumatiche/autoimmuni le differenze tra
uomini e donne sono rappresentate dalla:
diversa frequenza, gravità dei sintomi, decorso della
malattia, e risposta alla terapia.
Recenti evidenze di una differente risposta delle donne
rispetto agli uomini al trattamento con farmaci biologici quali
gli anticorpi anti-TNFα (usati per esempio nella terapia
dell’artrite reumatoide e delle malattie infiammatorie
croniche intestinali) indicano la forte necessità di costruire
percorsi terapeutici personalizzati in base al genere anche al
fine di un’ottimizzazione dei budget sanitari»
Marina Pierdominici - ISSM.Chagall. La passeggiata, 1917-1918
Le malattie autoimmuni coinvolgono circa il
5% della popolazione generale
Torino ∼ 878000 abitanti
∼ 43900 pazienti
Circa l'80% dei pazienti con malattie
autoimmuni sono donne
∼ 35100 pazienti
Dati ISTAT9:1 – 50:1 The role of gender and organ specific autoimmunity. U. Nussinovitch. Autoimmuity reviews 2011
Tale predominanza epidemiologica si riferisce a
una differenza di „sesso“ o di genere?
S. Oertelt-Prigione. Autoimmunity Reviews, 11, 2012.Systemic lupus erythematosus (SLE) SLE has a significant predominance in women. It tends to worsen during pregnancy and to remit after menopause. This suggests that sex hormones are crucial for SLE regulation. imbalance between hormone relationships with lower immune- suppressive androgens and higher immunoenhancing estrogens lower androgen levels than healthy women SLE-men with elevated serum levels of 16-hydroxyestrone and estrone hypoandrogenism, low levels of testosterone and elevated levels of luteinizing hormone (testosterone is thought to suppress anti-double stranded DNA antibody production) About 22-33% of SLE patients have mild to severe hyperprolactinemia. Prolactin leads to the production of interferon-gamma which is an important mediator in lupus nephritis. Bromocriptine, an inhibitor of prolactin secretion, has shown beneficial effects in both murines and humans.
Sjögren’s syndrome (SS) This disease is also one of the most prevalent ADs among women. SS primarily affects women during the fourth and fifth decades of life. In men SS is uncommon. Women with SS have more anti-Ro antibodies and Raynaud’s phenomenon than men. Men with SS are at higher risk for lymphoma and neurological involvement than women. Accordingly, male gender should be considered as a new risk factor for lymphoma development in patients with SS.
Journal of Autoimmunity 2012, 38; j109 - j119
Estrogens and androgens are hormones that have been studied for increasing susceptibility to Autoimmune Diseases. They can affect both innate and adaptive immune systems. • Estrogens seem to direct the immune system to T- helper 2 lymphocyte dominance more B cell activation and antibody production. • Androgen favors the development of a T-helper 1 response and CD8+ cell activation.
Tai-Ping Lee, et all. Autoimmunity rewiev 2012
Non così di corsa...
Secreetion of cytokines and chemokines
Macrophages Release of reactive oxygen species
Proliferation
T cells Adhesion to endothelial cells
Proliferation
B cells Secretion of IgM and IgG
Prolactin
Activation of STAT1 and MAPK pathways
Granulocytes Transcription of IRF-1 and iNOS
Proliferation and cytotoxic activity
Natural killr cells Release of IFN-Ƴ
Antigen presentation
Dendritic cells Expression of CD80/86 and MHC IIHyperprolactinemia and autoimmune deseases
Systemic diseases Organ-specific diseases
Type 1 diabetes
Multiple sclerosis
Systemic lupus erythematosus
Myasthenia gravis
Anti-phospholipid syndrome
Pemphigus vulgaris
Rheumatoid arthritis Psoriasis vulgaris
Psoriatic arthritis Celiac disease
Sjögren syndrome Autoimmune thyroid disease
Systemic sclerosis Autoimmune uveitis
Addison's disease
Behçet ́s disease
Lymphocytic hypophysitis
Reactive arthritis
Peripartum cardiomyopathy
Rejection of heart transplantationProlactin and autoimmunity. S. Shelly et al. Autoimmunity Reviews 11 (2012)
Le tre età della donna - G. Klimt, 1905
Other hormonal influences… Changes in the disease severity during menses and menopause are described. In young patients, an early age at menarche has been associated with doubling the risk of SLE and RA. Also the worsening of symptoms in RA, SLE and MS has been reported prior to the onset of menses. In older women, RA has a high incidence at menopause while onset of SLE is less common in postmenopausal women. The use of oral contraceptives in MS is associated with a decrease in disease incidence. In SLE, their use is associated with disease exacerbation and the safety of estrogens in lupus erythematosus national assessment (SELENA) study shows that hormone replacement therapy with estrogens can induce mild exacerbations.
Le tre età della donna - G. Klimt, 1905 (particolare)
Pregnancy… Signs and symptoms of MS and RA lessen during pregnancy and postpartum may be associated with disease exacerbation. SLE is often exacerbated during pregnancy and disease activity is associated with a worse fetal outcome. Pregnancy may induce changes in the maternal immune system in order to protect the fetus. A shift from the prevailing Th1 response to a type Th2 could be seen and attributed to an increased progesterone level. Also, pregnant women have enhanced immunoglobulin production and an increased production of autoantibodies. A worse pregnancy outcome has been found in SLE patients with glomerulonephritis being the main disease manifestation threatening both maternal and fetal health.
Le malattie autoimmuni: „dazio“ per un maggior
successo riproduttivo.
Regulatory T-cells and immune tolerance in pregnancy: a new target for infertility treatment? Human Reproduction 2008Il microchimerismo
Gender as risk factor for autoimmune diseases. Norbert Gleicher e all. Journal of autoimmunity 2007
E se la domanda
fosse…
Perché non gli
uomini?
Salvador Dali. Self Portrait as Mona Lisa. 1954Tali dati non sono univocamente accettati in letteratura; vi è però
consenso circa la maggior presenza di complicanze delle malattie
autoimmuni nei maschi.
C. Doukas et al, Rheumatol Int 2012 .Olga L. Quintero et all. Journal of Autoimmunity, 2012
G. de Chirico. Ettore e Andromaca, 1917
I fattori genetici
The female X-inactivation mosaic in systemic lupus erythematosuss. J.J. Stewart. Immunology today 1998
The female X-inactivation mosaic in systemic lupus erythematosuss. J.J. Stewart. Immunology
today 1998The female X-inactivation mosaic in systemic lupus erythematosuss. J.J. Stewart. Immunology
today 1998The X chromosome and the sex ratio of autoimmunity. Carlo Selmi e coll. Immunity Rewiev 2011
Epigenetics and Autoimmune Diseases. P.Q. Ronderos et all. Autoimmune Diseases 2012
E le differenze di genere?
L’importanza della dieta… L’esempio dell’emocromatosi in Sicilia per difetto del C282Y-gene. → Mutazione del gene HFE, C282Y, H63D a S65C → emocromatosi ereditaria → incapacità di formare un eterodimero con la beta2- microglobulina → abnorme assorbimento del ferro (da 2 a 3 volte) → dieta a basso introito di ferro (acarnea) per le donne a inizio ‘900 (carne come alimento solo per gli uomini) NO MALATTIA
K Razumof. 1974
Problema: esiste una correlazione tra lutilizzo del rossetto e linsorgenza delle malattie autoimmuni nel sesso femminile?
M.Chagall. La passeggiata, 1917-1918
…to be a woman is something so
strange, so confusing and so
complicated that only a woman
could put up with it.
KierkegaardGrazie per la
attenzione!
S. Dalì. La Venere di Milo con cassetti, 1936Puoi anche leggere
