General blood and urine tests
Changes in standard laboratory tests reflect the systemic nature of inflammation.
The complete blood count (CBC) often reveals anemia, which may be autoimmune, hemolytic, or post-hemorrhagic in nature (characteristic of systemic lupus erythematosus and rheumatoid arthritis). White blood cell counts vary in opposite directions: leukocytosis is observed in rheumatoid arthritis and vasculitis, whereas leukopenia is typical for SLE. The erythrocyte sedimentation rate (ESR) serves as a reliable marker of inflammatory activity and is used to monitor disease progression.
Of particular importance is the search for LE cells ("lupus erythematosus cells"). These are mature neutrophils that have engulfed the nucleus of a dead leukocyte, which displaces their own nucleus to the periphery. This phenomenon is observed in 3/4 of SLE patients. Additionally, hematoxylin bodies (destroyed nuclei) and the "rosette formation" phenomenon may be detected. However, LE cells are not strictly specific and sometimes appear in active chronic hepatitis, paraneoplastic reactions, or rheumatoid arthritis with systemic manifestations.
The urinalysis (UA) is used to screen for signs of nephropathy. The presence of protein (up to nephrotic syndrome), casts, and microhematuria indicates renal involvement, which is common in systemic diseases.
Immunological and serological markers
Immunological screening proceeds from ruling out infections to searching for autoantibodies.
- Association with infections: In reactive arthritides, antibodies to specific pathogens are sought (to Yersinia enterocolitica in post-yersiniotic arthritis, to Chlamydia trachomatis in Reiter's disease). An increase in antistreptococcal antibodies is typical for rheumatic fever-related arthritis, and markers of hepatitis B and C are checked when a viral etiology is suspected.
- Rheumatoid factor (RF): These are antibodies against the Fc fragment of IgG. It divides rheumatoid arthritis into seropositive and seronegative variants. However, RF is not entirely specific: it is elevated in SLE, scleroderma, infective endocarditis, tuberculosis, and even in healthy individuals.
- Anticardiolipin antibodies (aCL): Markers of antiphospholipid syndrome targeting negatively charged phospholipids. The syndrome manifests as thrombosis, strokes, livedo reticularis, thrombocytopenia, and recurrent pregnancy loss.
- Antineutrophil cytoplasmic antibodies (ANCA): Target neutrophil granule components (proteinase-3, myeloperoxidase). This is a highly specific criterion for systemic necrotizing vasculitides (e.g., granulomatosis with polyangiitis).
Immune status assessment and biochemistry
The intensity of immunopathological reactions is assessed using a number of parameters.
The total serum immunoglobulin level (primarily IgG) increases. The complement system responds sensitively to inflammation: its level rises in acute processes, while in active immune complex diseases (SLE, vasculitides) it decreases due to active consumption. Circulating immune complexes (CICs) appear in the blood and can also be detected in tissues using immunofluorescence. Cellular immunity is impaired: the number of T-lymphocytes typically decreases in autoimmune diseases.
Blood and urine biochemical analysis helps detect:
- Acute phase of inflammation: Elevation of C-reactive protein (CRP), fibrinogen, and seromucoid. Protein electrophoresis reveals hypergammaglobulinemia (especially pronounced in SLE and Sjögren's syndrome).
- Renal complications: Elevated creatinine signals renal failure secondary to glomerulonephritis (SLE) or amyloidosis (RA).
- Purine metabolism disorders: In gout, blood uric acid increases (hyperuricemia), along with its urinary excretion (hyperuricosuria).
Genetics and morphology
Additional methods confirm the diagnosis in complex cases.
In immunogenetics, the HLA-B27 antigen plays a crucial role. This marker is detected in 95% of patients with ankylosing spondylitis (Bechterew's disease) and indicates genetic predisposition.
For morphological diagnosis, biopsy samples of the synovial membrane, articular cartilage, muscles, or rheumatoid nodules are taken. If secondary amyloidosis is suspected, gum, rectal mucosal, or kidney tissues are examined.
Briefly: answers to topical questions
Which antibodies are most specific for diagnosing systemic lupus erythematosus?
The most specific antibodies for diagnosing systemic lupus erythematosus are anti-double-stranded DNA and anti-Smith antibodies.
Key diagnostic antibodies:
- Anti-double-stranded DNA antibodies (anti-dsDNA) — a highly specific criterion (scored as 6 points).
- Anti-Smith antibodies (anti-Sm) — a highly specific criterion (scored as 6 points).
- Antinuclear antibodies (ANA) — presence at a titer of ≥1/80 is a mandatory condition for diagnosis.
Additionally, diagnostics may reveal antibodies to extractable nuclear antigens (SS-A/Ro and SS-B/La), antibodies to ribonucleoproteins (anti-RNP), as well as antiphospholipid antibodies (anticardiolipin or β2-glycoprotein I).
To remember vasculitis specificity: ANCA is a marker of necrotizing vasculitides (granulomatosis with polyangiitis), and aCL is a marker of thrombosis (antiphospholipid syndrome).
Class and exam questions
Does the presence of rheumatoid factor always indicate rheumatoid arthritis?
No, rheumatoid factor can be present in systemic lupus erythematosus, scleroderma, infective endocarditis, tuberculosis, sarcoidosis, and even in low titers in healthy individuals.
What are LE cells and in which disease are they found?
These are mature neutrophils that have engulfed the nucleus of a destroyed leukocyte. They are detected in 75% of patients with systemic lupus erythematosus (SLE).
Why do complement levels decrease in systemic vasculitides and SLE?
A decrease in levels (hypocomplementemia) occurs due to the active consumption of complement components during immune complex reactions.
What else to study on this topic
- Pathogenesis of LE cell formation and the rosette phenomenon
- Mechanism of development of antiphospholipid syndrome and its clinical variants
- Differential diagnosis of seropositive and seronegative rheumatoid arthritis
- The role of immune complex pathology in renal involvement in rheumatic diseases
- The significance of the T-cell arm of immunity in the development of autoimmune processes
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