Compounds to Remember Flashcards
RAG1/2
recognizes RSS sequence and cleaves it (as a complex with HMG1)
HMG1
chromatin-binding protein (binds with RAG1/2) - required for rearrangement
Artemis
A nuclease that cleaves the hairpin structure of the coding joint (as a complex with Ku70,80/DNA-PKcs)
Ig alpha/beta
scaffolding protein for pre-BCR and BCR - required for successful signalling of rearrangement into the cell
TdT
unique to B cells; non-template, random addition of nucleotides to the end of the coding joint
ADA
an enzyme responsible for differentiation in early precursors of lymphovytes; deficiency leads to ADA-SCID (T- B- NK-)
BLNK
an adaptor protein; required for successful signalling of rearrangement into the cell
Syk and Btk
kinases; required for successful signalling of rearrangement into the cell
TRECS/KRECS
biproduct of succesful VDJ rearrangement in T/B cells
IVIg
purified IgG from pooled human sera (>1000 donors) using alcohol fractionation; dose is 400-600mg/kg per month in clinic; 2-4 hours per infusion
SCIg
Self-administered weekly subcutaneously via small pump; avoid peak/throughs of IVIg
CXCR5
chemokine receptor expressed by T cells that is upregulated after encountering antigen in lymphoid organ
CCR7
chemokine receptor expressed by B cells that is upregulated after encountering antigen in lymphoid organ
AID enzyme
- introduces nicks into the S DNA region of teh constant region of Ig gene (converting C to U bases) - creating double-stranded breaks
- introduces point mutations into V genes of GC B cells; important for somatic hypermutation
gp120
viral prtoein expressed by HIV that binds to CD4 in T cells to mediate viral entry; gp120/CD4 complex binds to CCR5/CXCR4 on host cell
Collagen/fibronectin
produced by Type A synoviocytes; contribute to structural framework of synovial interstitium and cell adherence
Hyaluronan
produced by Type A synoviocytes; high MW polysaccharide that maintains synovial fluid viscosity; procides shock absorption
Lubricin
mucin-like proteoglycan; protects cartilage surfaces from deposition and cell adhesion; inhibits synovial cell overgrowth
MMPs
matrix-metalloproteinases; degrades cartilage; produced by type B synoviocytes
IL-17
pro-inflammatory cytokine expressed by TH17 cells, induces expression of other pro-inflammatory cytokines and RANKL in other cells
TNF-alpha
expressed by activated macrophages, type B synoviocytes, and T cells; induces pro-inflammatory cytokine release, endothelial cell, osteoclast, and chondrocyte activation; angiogenesis
Increases number of osteoclast progenitors and increase expression of RANK and RANKL
Increase expression of DKK, decrease RUNX2 protein levels, alkaline phosphatase and osteocalcin
IL-1beta
inducible form of IL-1; highly pyrogenic and pro-inflammatory; activates leukocytes, endotthelial cells, synovial fibroblasts; induces expression of chemokines, sytokines; induces MMP production by chondrocytes, induces RANKL
produced by type B synoviovytes, macrophages, and endothelail cells, neutrophils
IL-6
pro-inflammatory cytokine, involved in fever and acute phase response; induce Ig production in B cells, induce differentiation of TH17 cells and osteoclast (RANKL induction), induce cytokine production
produces by macrophages, type B synoviocytes, and T cells
STAT3
phosphorylation by JAK receptors - leads to promotion of cytokine expression, supresses type B synoviocytes apoptosis; promote T cell survival, promote antibody production; promotes RANKL expression
RF
Rheumatoid factor; high-affinity autoantibody against Fc portion of IgG; prior to RA onset, an increase in IgM/IgA
DRB1 gene
encodes for HLA-DR antigen presenting molecule, allelic variants DRB1*0401/0404 most associated with RA
PADI
peptidyl-arginine deiminase; respondible for post-translational conversion of the amino acid arginine to citrulline (citrullination); PADI2/4 abundant in RA
ACPA
antibodies against citrullinated ‘self-proteins’; detected via anti-CCP assay; prior to RA onset, increase in SE spreasing and isotype changes
Hydroxypatite
Indoluble salt of calcium and phosphorus
RANKL
member of TNF family ligand - mostly membrane-bound but can be cleaved to a soluble form
induce osteoclast differentiation and activation; produced normally by osteoblasts and osteocytes
produced in RA mostly by type B fibroblasts, osteoblasts, T cells
RANK
receptor for RANKLS, expressed on osteoclasts and its precursors
Osteoprotegerin
member TNF-receptor family, binds RANKL (acts as decoy receptor); blocls RANKL-induces osteoclast differentiation and activation
Normally, produced by osteoblasts
IL-1
pro-inflammatory cytokine; promotes cell fusion of the mononuclear precursor cells and survival of mature osteoclast
Alkaline phosphatase
renders osteoid competent for mineral deposition
DKK
Wnt signalling antagonist; inhibition of Wnt signalling leading to inhibtion of osteoblast amturation and bone formation; expression increase by TNF
Methotrexate
a csDMARD, anti-metabolite, weekly oral dose; anchor drug, inital DMARD choice in majority of patient
Adverse effect: hepatotoxicity, myelotoxicity
Sulfasalazine
a csDMARD, anti-inflammatory and anti-microbial; twice daily oral dose
Side effect: hepatotoxicity, myelotoxicity
Hydroxycloroquine
a csDMARD; daily oral dose - side effect: retinopathy
Leflunomide
csDMARD, anti-metabolite; daily oral dose; side effects: hepatotoxicity, myelotoxicity, and hypertension
Adalimumab
Hman monoclonal antibody (IgG1); TNF inhibitor
Side effect: injection site reations, infections
Infliximab
chimeric antibody, huan IgG1 constant region and mouse vairbale region, anti-TNF
Side effect: injection site reations, infections
Etanercept
fusion protein: two p75 TNF-alpha receptors and human IgG1 constant region
Certolizumab pegol
humanised monoclonal antibody (anti-TNF), bound to polyethylene glycol (PEG)
Not inferior to ADA (when combined with MTX) in MTX-IR
Side effect: injection site reations, infections
Golimumab
human IgG1 monoclonal antibody against TNF
Side effect: injection site reations, infections
Abatacept
T-cell costimulation blocker; formed by CTLA4 molule dimerized on an Ig frame
non-inferior to ADA (ADA has more injection site reactions) in MTX-IR, b-DMARD naiive
Side effect: injection site reations, infections
Anankira
IL-1R antagonist
Side effect: injection site reations, infections
Rituximab
Chimeric monoclonal antibody (anti-CD20) leads to B cel depletion; doesn’t target B cells before Pre-B cell or after Memory B cell in the differentiation phases
non-inferior to ADA/ETA (more cost saving) in sero+ve, naiive RA patients
Side effect: injection site reations, infections
Tocilizumab
Humaized monoclonal antibody against IL-6R
Superior to ADA (but associated with more AE) in MTX-IR
Side effect: injection site reations, infections, elevated LDL, cytopenias(decrease in platelets and neutrophils)
Sarilumab
human IgG1 monoclonal antibody against IL-6R (soluble and membrane-bound)
Monotherapy was superior to ADA
Side effect: injection site reations, infections, neutropenia
JAK1/2
role in growth, neurodevelopment, haematopoesis, host defense
JAK3 and Tyk2
engaged in immune responses
Tofacitinib
oral JAK inhibitor; preferentially inhibit JAK1/3
limiting T cel and other leukocyte recruitment - decrease in synovial inflammation and structural damage
adverse effect: headaches, infection, elevated LDL. neutropenia
Baricitinib
Reversible inhibitor of JAK1/2
Side effects: neutropenia, increase in creatinine and LDL, infection risk, malignancy risk?
Upadacitinib
Selective inhibitor of JAK1
Adverse reactions: infection, headache, pulmonary embolism
