Graft-versus-host disease (GVHD) is a lethal complication of allogeneic hematopoietic stem cell transplantation (HSCT) where immunocompetent donor T cells attack the genetically disparate host cells. GVHD pathophysiology can be summerized in a three-step process. Step 1 involves the development of an inflammatory milieu resulting from damage in the host tissues induced by the preparative chemotherapy or radiotherapy regimen. Damaged tissues secrete inflammatory cytokines, including interleukin 1 (IL-1), and tumor necrosis factor (TNF-alpha ). During step 2, antigen-presenting cells (APCs) trigger the activation of donor-derived T cells, which induce further T-cell expansion, induce cytotoxic T lymphocytes (CTL) and natural killer (NK) cells responses and prime additional mononuclear phagocytes to produce TNF-alpha and IL-1. Also, nitric oxide (NO) is produced by activated macrophages, and it may contribute to the tissue damage seen during step 3. During step 3, the effector phase, activated CTL and NK cells mediate cytotoxicity against target host cells through Fas-Fas ligand interactions and perforin-granzyme B.
Category
Immune system disease
Brite
Human diseases in ICD-11 classification [BR:br08403]
04 Diseases of the immune system
Certain disorders involving the immune system
4B24 Graft-versus-host disease
H00084 Graft-versus-host disease
Pathway-based classification of diseases [BR:br08402]
Cellular process
nt06535 Efferocytosis
H00084 Graft-versus-host disease
Rheumatoid arthritis (RA) is a common autoimmune disease that primarily manifests as chronic inflammatory arthropathy. Persistent synovitis leads to cartilage destruction, bone erosions and periarticular decalcification, subsequently resulting in impaired joint function. It is more common between the ages of 35 and 50 years, affecting three times more women than men. Susceptibility to RA is genetically determined with multiple genes contributing. Inheritance of HLA DRB1 alleles encoding a distinctive five-amino-acid sequence known as the "shared epitope" (SE) is the best characterized genetic risk factor. The mechanism by which the SE alleles contribute to the development of RA is not very clear. It has been postulated that the presence of these conserved sequences in the antigen-binding groove alters the way antigenic peptides are bound to and presented to T-cell lymphocytes. This, in turn, may trigger abnormal immune responses and lead to RA.
Category
Immune system disease
Brite
Human diseases in ICD-11 classification [BR:br08403]
15 Diseases of the musculoskeletal system or connective tissue
Arthropathies
Inflammatory arthropathies
FA20 Rheumatoid arthritis
H00630 Rheumatoid arthritis
Pathway-based classification of diseases [BR:br08402]
Cellular process
nt06535 Efferocytosis
H00630 Rheumatoid arthritis
Tokuhiro S, Yamada R, Chang X, Suzuki A, Kochi Y, Sawada T, Suzuki M, Nagasaki M, Ohtsuki M, Ono M, Furukawa H, Nagashima M, Yoshino S, Mabuchi A, Sekine A, Saito S, Takahashi A, Tsunoda T, Nakamura Y, Yamamoto K
Title
An intronic SNP in a RUNX1 binding site of SLC22A4, encoding an organic cation transporter, is associated with rheumatoid arthritis.
Dawidowicz K, Allanore Y, Guedj M, Pierlot C, Bombardieri S, Balsa A, Westhovens R, Barrera P, Alves H, Teixeira VH, Petit-Teixeira E, van de Putte L, van Riel P, Prum B, Bardin T, Meyer O, Cornelis F, Dieude P
Title
The interferon regulatory factor 5 gene confers susceptibility to rheumatoid arthritis and influences its erosive phenotype.
Swanberg M, Lidman O, Padyukov L, Eriksson P, Akesson E, Jagodic M, Lobell A, Khademi M, Borjesson O, Lindgren CM, Lundman P, Brookes AJ, Kere J, Luthman H, Alfredsson L, Hillert J, Klareskog L, Hamsten A, Piehl F, Olsson T
Title
MHC2TA is associated with differential MHC molecule expression and susceptibility to rheumatoid arthritis, multiple sclerosis and myocardial infarction.
Suzuki A, Yamada R, Kochi Y, Sawada T, Okada Y, Matsuda K, Kamatani Y, Mori M, Shimane K, Hirabayashi Y, Takahashi A, Tsunoda T, Miyatake A, Kubo M, Kamatani N, Nakamura Y, Yamamoto K
Title
Functional SNPs in CD244 increase the risk of rheumatoid arthritis in a Japanese population.
