Áreas terapéuticas prioritarias en Inmunología

Muchas enfermedades inflamatorias inmunomediadas tienen limitadas o ninguna opción de tratamiento. Trabajamos para ayudar a los pacientes que viven con estas enfermedades debilitantes.

Sobre las enfermedades inflamatorias inmunomediadas

Gracias a nuestro sistema inmune innato y adaptativo, el ser humano está protegido de las infecciones por patógenos como bacterias, virus, hongos y parásitos. Estos sistemas de protección son diferentes entre sí, pero trabajan conjuntamente en nuestro organismo.

Muchas enfermedades inmunomediadas, como la artritis reumatoide, responden tanto de forma innata como adaptativa en diferentes estados de progresión de la enfermedad. El aspecto común de estas enfermedades es que son inmunomediadas, es decir, el sistema inmunitario es el principal factor causante de la inflamación. En AbbVie Immunology nos centramos en estas enfermedades inflamatorias inmunomediadas.

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Artritis

Artritis reumatoide

La artritis reumatoide (AR) es una enfermedad crónica, progresiva e inflamatoria cuya principal característica es la inflamación del revestimiento de las articulaciones. La AR causa inflamación, dolor articular, rigidez e hinchazón, pudiendo a veces causar daño permanente en las articulaciones.

La AR afecta aproximadamente al 1 % de la población adulta en el mundo industrializado (1,5 millones de estadounidenses)[1][2]. Las mujeres tienen tres veces más posibilidad de sufrir AR que los hombres [3].

La AR es una enfermedad inflamatoria inmunomediada crónica en la que el cuerpo ataca por error las articulaciones sanas, que con el paso del tiempo puede provocar una pérdida de función. [1]. A largo plazo, la AR puede degenerar en una capacidad reducida para realizar tareas y actividades diarias, como abrir un bote o girar el picaporte de una puerta.

Los tratamientos actuales para la AR se centran en la inhibición de componentes específicos del sistema autoinmune, lo que reduce la inflamación y ayuda a frenar la progresión de la AR. Más recientemente, los investigadores han observado que las diferentes señales del sistema inmunitario están activas a medida que progresa la enfermedad.

Estamos investigando diferentes áreas del sistema inmunitario asociadas a la AR con la esperanza de encontrar alternativas adicionales para interrumpir el curso de la enfermedad.[999]

Artritis idiopática juvenil

Artritis idiopática juvenil

La artritis idiopática juvenil (AIJ) es una enfermedad inflamatoria crónica inmunomediada que incluye varias formas de artritis crónica y afecta a niños de 16 años o menos [5][6]. Existen varios subtipos de AIJ y cada uno presenta síntomas diferentes: artritis sistémica, oligoartritis, poliartritis (factor reumatoide positivo o negativo), artritis psoriásica, artritis relacionada con entesitis y artritis indiferenciada.[6]

Aproximadamente 300.000 niños[7] en Estados Unidos y 59.000 en Europa[8] sufren AIJ, una enfermedad grave, dolorosa y potencialmente incapacitante que puede derivar en una incapacidad permanente[7]. Aunque la prevalencia dependa del subtipo, la AIJ suele producirse en mayor medida en niñas que en niños[9]. Algunos estudios han concluido que más de un tercio de los pacientes siguen desarrollando la enfermedad hasta la edad adulta.[10]

Los síntomas típicos de la AIJ son la rigidez al despertarse, cojera, sensibilidad articular, cansancio e inflamación de las articulaciones. Pueden verse afectadas varias articulaciones del cuerpo, como las rodillas, los tobillos y las articulaciones de manos y pies[5] y, en ocasiones, también afecta a órganos internos.[6] La inflamación derivada de la enfermedad puede limitar la movilidad de las articulaciones afectadas[11] y, en algunos casos más graves, puede causar problemas en el desarrollo óseo y el crecimiento.

El diagnóstico y tratamiento temprano de la AIJ son importantes para los pacientes que sufren esta enfermedad.

Ankylosing spondylitis

Ankylosing spondylitis

Ankylosing spondylitis (AS), or arthritis of the spine, is a chronic, multisystem inflammatory disorder. It primarily affects the spine, sacroiliac joints (where the spine meets the pelvis) and axial skeleton (the skull, rib cage and vertebrae). [12] The spine’s vertebrae begin to fuse together, causing spine rigidity, which leads to pain and stiffness from the neck down. [13] Symptoms can range from mild to severe. Over time, AS can result in a permanent stooped-over position. [13]

While the cause of AS is currently unknown, there is a strong genetic link. [13] AS affects approximately 0.1% to 0.5% of the adult population and, while it can occur at any age, it most commonly occurs in males in their teens or 20s. [13]

The most common symptom of AS is a gradual onset of lower back pain, [14] which includes ligament and tendon inflammation, constant pain and stiffness around the buttocks and hips and abnormal fusion of the vertebrae. [14] AS is a systemic disease, which can lead to more widespread symptoms such as fever, fatigue, loss of appetite and eye inflammation. In rare cases, lung and heart conditions may also arise.[14]

There is currently no cure for AS, but early diagnosis and treatment is important for patients with this condition.

Osteoarthritis

Osteoarthritis

Osteoarthritis (OA) is a disease of the entire joint—including the joint lining, cartilage, ligaments and bone. [15]

Osteoarthritis is the most frequent chronic musculoskeletal disease. There are at least 27 million adults afflicted with OA in the United States.[16] [17]Approximately 40 percent of adults over 70 are afflicted by OA of the knee and 25 percent are limited in their daily activities, making it the leading cause of disability in elderly persons.[17]

Osteoarthritis occurs most frequently in the hands, knees, spine, hips and toes. Symptoms of OA can include joint pain, stiffness, swelling, bone-on-bone noises when moving and limited joint mobility.[16] The cause of OA is not fully understood, although there are certain risk factors for the condition, including genetic predisposition, aging, obesity and joint malalignment.[17]

Cartilage degeneration in OA has been linked to interleukin-1 (IL-1), which exists as IL-1alpha (IL-1α) and IL-1beta (IL-1β), two closely related versions of the same molecule. [18] IL-1 is an inflammatory molecule, which may contribute to cartilage degradation.

Plaque psoriasis

Dermatology

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Plaque psoriasis

Plaque psoriasis is a chronic skin condition in which a person’s immune system sends faulty signals, resulting in skin cells that grow too rapidly. The body does not shed these excess skin cells, leading to a pile-up on the surface resulting in white, silvery or red patches of skin. The accumulation of these skin cells forms thick patches called “plaques” that typically appear on the knees, elbows, scalp, hands, feet and lower back. [19]

There is strong evidence that plaque psoriasis may be genetically inherited, although it can be triggered by external environmental factors such as cold and dry climates, infections, stress, dry skin and certain medications. Additionally, physical injury to the skin can cause more patches to form.[19] Most common in adults, plaque psoriasis is not contagious and cannot be spread by touch.[19] Plaque psoriasis is a common disease, affecting approximately 2% of the global population [20] (over 125 million people worldwide [21] and 7.5 million people in the United States [22]). Patients with plaque psoriasis sometimes develop psoriatic arthritis or similar conditions. [21]

The extent and duration of symptoms in plaque psoriasis varies greatly from patient to patient. Symptoms tend to disappear, even without treatment, and can flare up without warning. [19]

In more severe cases of plaque psoriasis, the skin becomes inflamed, itchy and tender. These patches can join together and cover large areas of skin such as the back.[19] Patients with plaque psoriasis may become self-conscious and avoid activities that would expose their skin, such as swimming [23].

Approximately 10 to 20% of patients with plaque psoriasis also experience psoriatic arthritis, inflammation of the joints that can progress to severe deformities. [23]

Psoriatic arthritis

Psoriatic arthritis

Psoriatic arthritis is a chronic inflammatory disease that targets healthy joints and skin. It affects up to 30 percent [24] of the estimated 125 million people worldwide with psoriasis. [21] Psoriatic arthritis combines skin symptoms such as dry, scaly skin and patches of red, raised skin known as “plaques” with arthritis symptoms, including joint pain and inflammation. Many people also have pitting of their fingernails or toenails. [25]

Psoriatic arthritis can be difficult to diagnose, particularly in its milder forms and earlier stages. [26] However, early diagnosis is important for preventing long-term damage to joints and tissue. [27]

The disease affects men and women almost equally and usually occurs between the ages of 36 and 40, [24] but it can develop at any age. Family studies suggest that up to 40% of people with psoriatic arthritis have a close relative that also has the disease. [28] Researchers have also discovered certain genetic factors that appear to be associated with psoriatic arthritis. [28]

Hidradenitis suppurativa

Hidradenitis suppurativa (HS) is a painful, chronic inflammatory skin disease characterized by inflamed areas typically located around the armpits and groin, on the buttocks and under the breasts. [29] Physical signs include painful abscesses and nodules, sinus tracts and scarring. [30][31]

HS is often under recognized and misdiagnosed; average diagnosis time can be lengthy. [32][33] Signs and symptoms of HS include deep-seated lesions consisting of painful nodules and abscesses, lesions localized to the armpit, groin, buttocks and breast regions of the body and recurrences over time. [32]

The average onset of HS usually occurs after puberty, typically during the second or third decade of life. [34] HS can be progressive and increase in severity over time. Early diagnosis and management is important. [35]

Crohn’s disease

Inflammatory Bowel Disease

Crohn’s disease

Crohn’s disease (CD) is a chronic, inflammatory bowel disease (IBD) that can affect anywhere along the digestive tract, from the mouth to the anus.[36] In CD, mucosal lesions are caused by inflammation that penetrates the full thickness of the bowel wall. Common symptoms of the disease include diarrhea, cramps/abdominal pain, weight loss and fever.[36]

CD affects approximately 565,000 people in the United States.[37]Men and women are equally affected,[38] with a higher prevalence seen in North America and Europe.[39] People of all ages can suffer from CD, but it is most often diagnosed in adolescents and young adults between the ages of 15 and 35.[39]

CD is characterized by periods in which the disease flares and periods of remission, during which symptoms decrease or disappear.[40]Complications of CD can include fistulas (ulcers in the wall of the intestine that cause a tunnel to another part of the intestine, skin or another organ), stricture, which can lead to intestinal obstruction or an abscess.[40]

Ulcerative colitis

Ulcerative colitis

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) that causes ulcers in the colon and rectum.[41] While Crohn’s disease can affect any part of the gastrointestinal tract, UC only affects the colon and rectum, resulting in diarrhea, rectal bleeding, abdominal cramping and weight loss.[42] UC only affects the innermost lining of the intestinal wall.[42]

Up to 700,000 Americans may be living with UC. [42]  Typically, people are diagnosed with UC in their mid-30s, though the disease can occur at any age. [42]  Patients may experience a range of symptoms based on the extent of the disease and severity of inflammation. [42] The symptoms tend to come and go, with periods of clinical stability punctuated by episodic flares of disease activity. [42] Severe flares of UC can necessitate hospitalization and may lead to life-threatening complications. [43]

It is estimated that 25 to 33% of patients with UC may require surgery during their lifetimes. Over the long term, UC can increase the risk of colon cancer. In addition, some patients may experience symptoms in other parts of the body such as joint pain, eye problems and liver disease. [44]

Systemic lupus erythematosus

Systemic lupus erythematosus

Systemic lupus erythematosus (SLE), the most common type of lupus, is associated with inflammation of multiple organ systems throughout the body[45]. Diagnosis of lupus is challenging due to a range of symptoms that can affect the kidneys, lungs, skin, nervous system and musculoskeletal system.

A report submitted by the National Arthritis Data Working Group estimated that SLE affects 250,000 Americans and is more common in females of childbearing age; however, it can affect men or women at any age. The highest prevalence occurs in women, African-Americans and persons between 20 and 40 years of age.[45] Although the cause of SLE is not known, it can be triggered by exposure to sunlight and certain drugs. A potential genetic link has been identified, in which people who carry a specific form of the genes for both Bcl-2 and IL-10, an immune signaling molecule, are at significant risk of developing SLE.[46] In many cases an autoimmune reaction, where the immune system attacks itself, may be present and detectable years before the symptoms are apparent. This increase in autoimmune activity is helpful in diagnosing the disease.[47]

Although SLE is often associated with inflammatory arthritis and a butterfly-shaped facial rash, it is more common for individuals with SLE to have other symptoms. These can include fatigue, malaise (a general feeling that you aren’t well), oral ulcers, skin rashes that appear after exposure to sunlight, chest pains, headache, sensations of burning, tickling or itching on the skin, dry eyes and mouth, discoloration of toes and fingers in the cold and mild hair loss. There can also be a problem with any one of a patient’s major organs.[47]

[1] National Institute of Arthritis and Musculoskeletal and Skin Diseases. Handout on Health: Rheumatoid Arthritis. 2014. http://www.niams.nih.gov/health_info/rheumatic_disease /. Accessed May 25, 2016.

[2] Brennan FM, McInnes IB. Evidence that cytokines play a role in rheumatoid arthritis. J Clin Invest. 2008;118(11):3537-3545.

[3] Van Vollenhoven RF. Sex differences in rheumatoid arthritis: more than meets the eye. BMC Med. 2009;7(1):12.

[4] Srikesavan CS, Shay B, Szturm T. Test-retest reliability and convergent validity of a computer based hand function test protocol in people with arthritis. Open Orthop J. 2015;9:57-67.

[5] Southwood T, Szer I. Juvenile Idiopathic Arthritis. In: ABC of Rheumatology. Vol Wiley; 2010:Chapter 15. https://books.google.com/books?id=ehnQn0VZZ3kC&pg=PT201&lpg=PT201&dq=abc+of+rheumatology+juvenile+idiopathic+arthritis&source=bl&ots=wKwH_awciB&sig=Hhc01Wt9Mmrd8QiqqTvgjhe4sxo&hl=en&sa=X&ved=0CDgQ6AEwAmoVChMI59j_tvu3xwIViReSCh1JOgjL#v=onepage&q=abc. Accessed May 25, 2016.

[6] National Institute of Arthritis and Musculoskeletal and Skin Diseases. Questions and Answers About Juvenile Arthritis. 2015. http://www.niams.nih.gov/Health_Info/Juv_Arthritis/default.asp. Accessed May 25, 2016.

[7] Chang HJ, Burke AE, Glass RM. Juvenile idiopathic arthritis. JAMA. 2010;303(13):1328.

[8] Thierry S, Fautrel B, Lemelle I, Guillemin F. Prevalence and incidence of juvenile idiopathic arthritis: a systematic review. Joint Bone Spine. 2014;81(2):112-117.

[9] Centers for Disease Control and Prevention. Childhood Arthritis. 2013. http://www.cdc.gov/arthritis/basics/childhood.htm. Accessed May 25, 2016.

[10] Malviya A, Johnson-Lynn S, Avery P, Deehan D, Foster H. Juvenile idiopathic arthritis in adulthood and orthopaedic intervention. Clin Rheumatol. 2009;28(12):1411-1417.

[11] Ding T, Hall A, Jacobs K, David J. Psychological functioning of children and adolescents with juvenile idiopathic arthritis is related to physical disability but not to disease status. Rheumatology. 2008;47(5):660-664.

[12] Daikh DI, Chen PP. Advances in managing ankylosing spondylitis. F1000Prime Rep. 2014;6:78.

[13] WebMD. Arthritis and Ankylosing Spondylitis. 2015. http://www.webmd.com/back-pain/guide/ankylosing-spondylitis. Accessed May 25, 2016.

[14] Brent LH. Ankylosing Spondylitis and Undifferentiated Spondyloarthropathy. Medscape. 2015. http://emedicine.medscape.com/article/332945-overview. Accessed May 25, 2016.

[15] Srikulmontree T. Osteoarthritis. Am Coll Rheumatol. http://www.rheumatology.org/I-Am-A/Patient-Caregiver/Diseases-Conditions/Osteoarthritis/. Accessed May 25, 2016.

[16] Lawrence R, Felson D. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States: Part II. Arthritis Rheum. 2008;58(1):26-35.

[17] Oliviero F, Ramonda R, Punzi L. New horizons in osteoarthritis. Swiss Med Wkly. 2010;140:w13098.

[18] Lee AS, Ellman MB, Yan D, et al. A current review of molecular mechanisms regarding osteoarthritis and pain. Gene. 2013;527(2):440-447.

[19] WebMd. Psoriasis – Topic Overview. 2015. http://www.webmd.com/skin-problems-and-treatments/psoriasis/understanding-psoriasis-basics. Accessed May 26, 2016.

[20] World Health Organization. Psoriasis.; 2013. http://apps.who.int/gb/ebwha/pdf_files/EB133/B133_5-en.pdf. Accessed May 26, 2016.

[21] Langham S, Langham J, Goertz H-P, Ratcliffe M. Large-scale, prospective, observational studies in patients with psoriasis and psoriatic arthritis: A systematic and critical review. BMC Med Res Methodol. 2011;11(1):32. doi:10.1186/1471-2288-11-32.

[22] American Academy of Dermatology. Psoriasis. 2015. https://www.aad.org/media-resources/stats-and-facts/conditions/psoriasis. Accessed May 26, 2016.

[23] Lui H. Plaque Psoriasis. Medscape. 2015. http://emedicine.medscape.com/article/1108072-overview. Accessed May 26, 2016.

[24] Gladman DD. Psoriatic arthritis. Dermatol Ther. 22(1):40-55.

[25] Angelillo MP. Psoriatic Arthritis. In: All About Arthritis. Vol iUniverse; 2009:40-45. https://books.google.com/books?id=_Gch5mIlSsYC&pgis=1. Accessed May 25, 2016.

[26] National Psoriasis Foundation. Tests to confirm diagnosis of psoriatic arthritis. 2015. https://www.psoriasis.org/psoriatic-arthritis/diagnosis/tests-to-confirm. Accessed May 15, 2016.

[27] National Psoriasis Foundation. About Psoriatic Arthritis. 2015. https://www.psoriasis.org/about-psoriatic-arthritis. Accessed May 25, 2016.

[28] Genetics Home Reference. U.S. National Library of Medicine. Psoriatic arthritis. August 2015. http://ghr.nlm.nih.gov/condition/psoriatic-arthritis. Accessed May 25, 2016.

[29] Jemec GBE. Hidradenitis Suppurativa. N Engl J Med. 2012:366:158-164.

[30] Dufour DN, Emtestam L, Jemec GB. Hidradenitis Suppurativa: A Common and Burdensome, Yet Under-Recognised, Inflammatory Skin Disease. Postgrad Med J. 2014; 90 (1062):216-21.

[31] Esmann S, Jemec GB. Psychosocial impact of hidradenitis suppurativa: a qualitative study. Acta dermato-venereologica. 2011;91(3):328-332.

[32] L.J. Margesson, F.W. Danby. Hidradenitis suppurativa. Best Pract Res Clin Obstet Gynaecol. 2014; 28: 1013-1027.

[33] Dhaou BB, Boussema F, Aydi Z, Baili L, Rokbani L. Hidradenitis suppurativa (Verneuil’s disease). J Saudi Soc Dermatology & Dermatol Surg. 2013;17:1-5.

[34] American Academy of Dermatology. Hidradenitis suppurativa. Available at: https://www.aad.org/public/diseases/painful-skin-joints/hidradenitis-suppurativa. Accessed May 25, 2016.

[35] Collier F, Smith RC, Morton, CA. Diagnosis and management of hidradenitis suppurativa. BMJ. 2013;346.

[36] U.S. National Library of Medicine. National Institutes of Health. Crohn’s Disease. 2015. http://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0022801/. Accessed May 25, 2016.

[37] Kappelman MD, Moore KR, Allen JK, Cook SF. Recent trends in the prevalence of Crohn’s disease and ulcerative colitis in a commercially insured US population. DigDis Sci. 2013;58:519-525.

[38] Crohn’s & Colitis Foundation of America. What is Crohn’s Disease? 2015. http://www.ccfa.org/what-are-crohns-and-colitis/what-is-crohns-disease/. Accessed May 25, 2016.

[39] Molodecky NA, Soon IS, Rabi DM, et al. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology. 2012;142(1):46-54.e42; quiz e30.

[40] Crohn’s & Colitis Foundation of America. The Facts About Inflammatory Bowel Diseases. 2014. http://www.ccfa.org/assets/pdfs/updatedibdfactbook.pdf. Accessed May 25, 2016.

[41] U.S. National Library of Medicine. National Institutes of Health. Ulcerative Colitis. 2015. http://www.nlm.nih.gov/medlineplus/ulcerativecolitis.html. Accessed May 26, 2016.

[42] Crohn’s and Colitis Foundation of America. What is Ulcerative Colitis? 2015. http://www.ccfa.org/what-are-crohns-and-colitis/what-is-ulcerative-colitis/. Accessed May 26, 2016.

[43] Mayo Clinic. Ulcerative colitis. 2015. http://www.mayoclinic.org/diseases-conditions/ulcerative-colitis/basics/definition/con-20043763. Accessed May 26, 2016.

[44] Crohn’s & Colitis Foundation of America. Living with Ulcerative Colitis. http://www.ccfa.org/assets/pdfs/living_with_uc_brochure_final.pdf. Accessed May 26, 2016.

[45] Maidhof W, Hilas O. Lupus: an overview of the disease and management options. P T. 2012;37:240-249.

[46] Mehrian R, et al. Synergistic effect between IL-10 and bcl-2 genotypes in determining susceptibility to systemic lupus erythematosus. Arthritis Rheum. 1998 Apr;41(4):596-602

[47] D’Cruz DP. Systemic lupus erythematosus. BMJ. 2006;332(7546):890-894.