I. Anti-nuclear antibodies
1. Anti-nuclear antibodies (ANAs)
Antibodies against nuclear components of cells present in the patient’s serum that can specifically bind to nuclear antigen components to form antigen-antibody complexes. Broadly speaking, they are anti-nucleic acids and nuclear proteins, i.e. DNA, RNA and the proteins bound to them.
Immunofluorescence assays generally use Hepo-2 cells that
Clinical significance.
Homogeneous (Homogeneous): associated with anti-histone antibodies and anti-DNA. Any type of antibody with a high titer can also be homogeneous
Peripheral Membrane-type: Anti-double-stranded DNA antibodies correspond to this type and are most commonly seen in patients with lupus nephropathy
Speckled type (Speckl): associated with anti-ENA
Nucleolar: These are associated with ribosomal antibodies in the nucleus and are most often seen in patients with SLE
Centromere: mainly associated with Raynaud’s phenomenon and SSc, once thought to have a high specificity with CREST.
ANA is mainly a screening test for rheumatic diseases, and ANA > 1:80 is clinically relevant. positive ANA antibodies may not have a parallel relationship with disease activity. Low titers of ANA can be seen in infections, tumors and normal subjects.
2. Anti-DsDNA antibodies
Anti-dsDNA antibodies have a high specificity for the diagnosis of SLE and parallel the activity of SLE. It has been shown that this antibody binds to DNA to form an immune complex that is deposited in the glomerular basement membrane or acts directly on glomerular antigens to cause kidney damage in SLE patients.
3. Anti-histone antibodies (anti-histone)
Anti-histone antibodies are found in a variety of rheumatic diseases, with a positive rate of more than 90% in drug-resistant lupus, and the highest titers of anti-histone antibodies are found in patients taking isoniazid and SLE.
IgG type anti-histone antibodies are predominant in SLE, while IgM type is predominant in patients on long-term isoniazid and RA.
Other drugs that can cause lupus include hydrazinoprazine and procainamide, as well as anti-arrhythmic and anti-hypertensive drugs.
4.Anti-ENA antibodies (extractable nuclear antigen)
Antigen-antibody reactions include: precipitation and agglutination reactions, and soluble antigen-antibody reactions are precipitation reactions.
ENA extractable nuclear antigen, which is soluble in saline, is an acidic nuclear protein. The main components include: U1RNP, Sm, SSA, SSB, Scl-70, Jo-1, rRNP, etc. Currently, immunodouble diffusion (ID) and immunoblotting (IBT) methods are generally used, but ID is more reliable.
(1) Anti-nRNP (nuclear RNP antibody): the antigen is a ribonucleoprotein containing uracil, mainly in the nucleus. The more used is U1RNP antibody, which is almost positive in MCTD and has a high titer (more than 1:64). and is closely associated with pulmonary hypertension. Raynaud’s phenomenon, myositis and dactylosclerosis. It is also seen in lupus and scleroderma.
(2) Anti-Sm antibodies (small uracil-rich SnRNP in the nucleus). Antigenic protein with molecular weights of 29, 28, 13.5 kD, highly specific for the diagnosis of SLE, a marker antibody for SLE, and generally not correlated with disease activity.
PS: RNP is mainly U1, while Sm includes U1, U2, U4, U6, so the presence of RNP does not necessarily mean that there is anti-Sm antibody, but there must be RNP if there is Sm antibody. 60% of anti-U1RNP antibody has cross-reactivity with 28/29kD of anti-Sm antibody, so only 28/29kD is positive, which does not indicate anti-Sm positivity.
(3) Anti-SSA/Ro antibodies: The antigen is mainly found in the cytoplasm and has a molecular weight of 52 KD and 60 KD. 52 KD peptide bands are associated with SS, while 60 KD peptide bands are more commonly seen in SLE patients. associated.
(4) Anti-SSB/La antibodies (also known as Ha antibodies): associated with SS and more specific than anti-SSA antibodies in the diagnosis of SS.
Anti-SSA positivity and anti-SSB positivity can cause neonatal lupus (mainly skin, platelet manifestations) and congenital AV block (usually third degree), and are often associated with vasculitis, lymph node enlargement, leukopenia, photosensitivity, skin lesions, and purpura.
(5) Anti-rRNP antibodies: (antigen is a phosphoprotein present in the cytoplasm) are often present during the active phase of SLE and are associated with central nervous symptoms (wolf brain, digestive system involvement). Unlike anti-dsDNA, anti-rRNP antibodies do not disappear immediately with remission and can persist for 1-2 years before turning negative.
(6) Anti-Scl-70 antibody: (antigen is DNA topoisomerase) This antibody is highly specific for the diagnosis of SSc and positive patients are at high risk of interstitial lung lesions.
(7) Anti-Jo-1 antibody: (antigen is anti-histidine tRNA synthetase) Currently considered a marker antibody for polymyositis/dermatomyositis.
Anti-Jo-1 antibody syndrome: myositis combined with interstitial lung lesions, symmetrical arthritis, “mechanic’s hand”, Raynaud’s phenomenon, fever.
(8) Anti-PCNA antibody: Anti-value-added cell nucleus antibody. Double diffusion method has a positive rate of 3-5% in patients with SLE.
(9) Anti-Ku antibodies: mostly seen in PM and SSc, also seen in MCTD, SLE
(10) Anti-PM-Scl antibody: mainly found in patients with overlapping PM/DM and SSc, with a positive rate of 87% in patients with overlapping PM/DM and SSc with nephritis.
5.Anti-synaptic antibody (ACA)
The antigens are 17kD, 80kD, and 140kD proteins of the chromosomal granule region.
This antibody is present in 80% of Crest syndrome (calcinosis cutis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia soft tissue calcification, Raynaud’s phenomenon, esophageal dysfunction, finger end sclerosis, capillary (dilation) have this antibody.
ACA is associated with liver damage in SS.
6.Anti-nucleus accumbens antibody: related to SSc
7, anti-DNP antibody (anti-nucleosome antibody).
An antibody against a group of protein complexes of DNA that can be used as an alternative to the lupus cell (LE) test.
Screening test for SLE. The positive rate is 80-90% in the active phase of SLE and 20% in the inactive phase.
II. Antiphospholipid antibodies
Antiphospholipid antibodies ( antiphospholipid antibodies, APL): antibodies against various negatively charged phospholipids, including
anticardiolipin antibody (ACL), false-positive syphilis serologic test
lupus anticoagulant (LAC), the
anti-phosphatidylserine, anti-phosphatidylglycerol, anti-phosphatidylglycerol, anti-phosphatidic acid and anti-β2-GP1.
Common diseases.
SLE, habitual abortion, neurological disorders, acute and chronic leukemia, thrombosis, thrombocytopenia.
Closely related to these diseases with altered coagulation system, thrombosis, thrombocytopenia.
Antigenic in phospholipid genes: cardiolipin, phospholipid base, acyl serine, acyl inositol lipid and acyl ethanol lipid.
2-GP1 (apolipoprotein) binds to phospholipids, exposing them to recognized epitopes, and exhibits phospholipid antibody properties. β2-GP1 is an essential cofactor
1. Anti-cardiolipin antibodies-ACL
ACL is a group of non-homogeneous antibodies with different characteristics, mainly of three types: IgG, IgM and IgA.
Two types: one is non-β2-GP1-dependent antibodies, mostly seen in infectious diseases.
One type is β2-GP1-dependent antibodies, mostly seen in autoimmune diseases
High level of IgG type: specific diagnosis of APS
20-50% positive rate in SLE: IgG and IgM types
Thrombosis, miscarriage and thrombocytopenia: IgG types
Hemolytic anemia and neutropenia: IgM type
SS: high incidence of IgA type
IgA: associated with habitual abortion and severe Grin-Barre syndrome.
2. Lupus anticoagulant – LAC
LAC is an antibody that prolongs the clotting time. The antibody can be IgG and IgM type or both coexist.
LAC has the highest positivity rate in patients with lupus.
It can be seen in: ITP, true erythrocytosis, streptococcal infection, malignancy, hepatitis and taking phenothiazines
3. Anti-β2-GP1 antibodies.
Anti-neutrophil cytoplasmic antibodies
(antineutropil cytoplasmic antibodies, ANCA)
ANCA represents a spectrum of antibodies against cytoplasmic components of neutrophils, with antigenic components including
Human neutrophil proteinase 3 (PR-3), myeloperoxidase (MPO), bactericidal/permeability enhancing protein (BPI), serine oxidase, human albumin elastase (HLE), lactoferrin (LF), histonectin G (CG), β-glucuronidase, lysozyme, etc.
Under fluorescence microscopy ANCA is divided into cytoplasmic ANCA (C-ANCA – the main antigenic component is PR-3) and perinuclear type (P-ANCA – the main antigenic component is MPO) based on fluorescence distribution, and the third type is atypical ANCA (X-ANCA)
1. The specificity of C-ANCA-WG is 95%
Associated with C-ANCA include: Wegener’s granulomatosis (WG), additionally detected in polyarteritis nodosa (PAN), microscopic polyangiitis (MPA).
2.P-ANCA
P-ANCA is mainly associated with MPA, NCGN, and Churg-Slrauss Syndrome. MPO-ANCA can also be seen in other diseases such as PAN, anti-glomerular basement membrane disease (anti-GBM disease), WG, SLE, RA, drug-resistant lupus, and Felty syndrome.
In addition, 8% of drug-resistant lupus in SLE and a higher percentage of drug-resistant lupus have anti-MPO positivity.
Rheumatoid factor (RF)
RF is an autoantibody against the Fc fragment of the degenerate IgG molecule and can be classified as IgM-RF, IgG-RF, IgA-RF, IgE-RF. Persistent high titers of RF often indicate RA activity and a high incidence of bone erosion.
IgM-RF is associated with subcutaneous nodules, vasculitis, lower extremity ulcers, and multiple mononeuropathies in RA and is highly correlated with HLA-DR4 and HLA-DR1.
IgG-RF is associated with extra-articular symptoms of RA and activity of RA
IgA-RF is associated with RA secondary to IgA nephropathy and dry syndrome
IgE-RF is associated with RA in combination with vasculitis.
Clinical significance.
1, the positive rate of RF in RA is about 80%, and is an important serological criterion for the diagnosis of RA
2, seen in many autoimmune diseases: SS (50%), SLE (30%), scleroderma (SSc), polymyositis/dermatomyositis (PM/DM)
3, Infectious diseases: bacterial endocarditis, tuberculosis, leprosy, schistosomiasis
4, Non-infectious diseases: diffuse interstitial lung fibrosis, nodular disease, macroglobulinemia
RA-specific factors
1, APF (antiperinuclear factor), the target antigen is located in the perinuclear granules of human buccal mucosal cells. Positivity correlates with disease and often suggests a poor prognosis.
2, AKA (antikeratin antibody) anti-keratin antibody. Associated with severity and activity.
3, anti-Sa antibody: morning stiffness in positive group, joint involvement is significantly heavier than in negative group
4.anti-RA33/36 antibody: sensitivity 35.8%, specificity 99.6%
5.Anti-cyclic citrullinated polypeptide (CCP) antibody.