1st order laboratory parameters – obligatory laboratory tests.
- Small blood count
- Differential blood count
- Inflammatory parameters – CRP (C-reactive protein) or ESR (erythrocyte sedimentation rate):
- CRP is a biomarker for diagnosis and at the same time for evaluation of disease activity of rheumatoid arthritis [mildly to moderately elevated CRP levels]
- CRP may play an important role in bone destructive processes of rheumatoid arthritis through the induction of RANKL expression, i.e., in the direct differentiation of osteoclast precursors into mature osteoclasts (osteoclast genesis).
- ESR (erythrocyte sedimentation rate): [elevated; > 10 mm]
- Urine status (rapid test for: nitrite, protein, hemoglobin, erythrocytes, leukocytes) incl. sediment, if necessary urine culture (pathogen detection and resistogram, that is, testing of suitable antibiotics for sensitivity / resistance).
- Serum electrophoresis
- Anti-citrulline antibodies – antibodies against cyclic citrullinated peptides (ACPA, CCP-Ak, anti-CCP) [highest disease specificity and sensitivity! ], these in combination with rheumatoid factors can increase the reliability of diagnosis at an early stage of the disease. Anti-citrulline antibodies are directed against proteins containing the rare amino acid citrulline. It has been demonstrated that the affected articular mucosa of patients with rheumatoid arthritis secretes citrullinated proteins, which may be responsible for the inflammatory response and tissue destruction. Already in the early stages of RA, CCP-AK* are detectable in about 80 % (sensitivity (percentage of diseased patients in whom the disease is detected by the use of the test, i.e. a positive test result occurs) approx. 75 %; specificity approx. 96 %). Thus, positive CCP-AK in diagnostically unclear cases and rheumatoid factor-negative patients represent a considerable diagnostic gain. Detected CCP-AK are almost considered proof of rheumatoid arthritis.
- Rheumatoid factor* (RF; see below) [the sole determination of the RF for the diagnosis of rheumatoid arthritis is to be rejected according to current knowledge!]
- ANA (antinuclear antibodies).
* Common occurrence is associated with a worse prognosis.
Rheumatoid factor (RF)
- Rheumatoid factor (RF) is autoantibodies that are detectable in more than two-thirds of people with the disease – however, 5% of healthy people also have positive rheumatoid factor and the frequency increases with age.If rheumatoid factor is detectable, it is called seropositive rheumatoid arthritis.
- In addition, there are a number of diseases besides rheumatoid arthritis in which a positive rheumatoid factor is detectable. These include systemic lupus erythematosus, Sjögren’s syndrome, chronic liver disease, sarcoidosis, interstitial pulmonary fibrosis, infectious mononucleosis, hepatitis B, tuberculosis, leprosy, syphilis, subacute bacterial endocarditis, visceral leishmaniasis, schistosomiasis and malaria.
- Furthermore, a positive rheumatoid factor may occur in healthy individuals after an infusion or receipt of a blood transfusion.
- Occasionally found in relatives of individuals with rheumatoid arthritis.
- Rheumatoid factor can be used to estimate prognosis, as patients with high titers tend to have a more severe and rapidly progressive disease course.
- A positive rheumatoid factor does not necessarily mean that rheumatoid arthritis is present. On the other hand, a negative rheumatoid factor does not exclude rheumatoid arthritis either (sensitivity is 60-80% and specificity is 90%).
In the context of rheumatoid arthritis, various inflammatory parameters are checked. These represent a non-specific sign of inflammation, although they alone can not confirm the presence of rheumatoid arthritis. They generally correlate with disease activity – that is, the higher the inflammation levels, the higher the likelihood of progressive joint damage. Other laboratory parameters include:
- IL-1, TNF-alpha, IL10, IL12, IL-1- receptor antagonist (IRAP), ICAM-1, metalloproteinases (MMPs), cathepsins, osteocalcin – these parameters are of scientific interest rather than suitable for routine diagnostics
- Cartilage Oligomeric Matrix Protein (COMP) – biomarker for articular cartilage destruction.Fragments of the protein are released by inflammatory, traumatic or degenerative processes at the articular cartilage. In rheumatoid arthritis, an elevated value indicates active cartilage degradation, an important prognostic criterion for radiologically measurable destruction.
- Autoantibodies to RA33 (hnRNP-A2) – RA 33 antibodies are associated with a mild disease course.
Laboratory parameters 2nd order – depending on the results of the history, physical examination, etc. – for differential diagnostic clarification.
- HLA-B27 – indication of spondyloarthritides (inflammatory rheumatic disease with predominant involvement of the spine: sacroiliac joints (sacroiliitis) and spine (syndesmophytes, spondylitis)).
- HLA-DR4 and HLA-DR1 (shared epitopes, a common gene segment) – found more often in patients with rheumatoid arthritis.
- HLA-DRB1 – when the amino acid valine at position 11:
- Present on both HLA-DRB1 proteins (homozygous; carrier): 74% of patients had severe joint destruction within five years.
- Heterozygous trait carriers: 61%.
In patients with a different amino acid at position 11 (non-carriers), disease progressed rapidly in only 48% of patients.
- Uric acid/joint puncture – to differentiate polyarthricular gout and infectious arthritides (joint inflammation).
- Antineutrophil cytoplasmic antibody (ANCA) – indication of vasculitides (vascular inflammation).
- Synovial analysis
- Autoimmune serology Antinuclear antibodies (ANA), antibodies against extractable antigens (ENA), anti-cardiolipin antibodies, anti-citrulline antibodies (see above).
- Screening for cardiovascular disease (regular).
