Rheumatoid arthritis (RA) is a chronic, inflammatory, autoimmune disease that impacts approximately 0.5-1% of the adult population and presents two- to three-fold more frequently in women than in men 1. RA with a symptom duration of fewer than six months is defined as early RA, and when the symptoms have been present for more than six months, it is described as established RA 2. There is no pathognomonic laboratory test for rheumatoid arthritis, making diagnosis challenging in the early stages. A comprehensive clinical approach is required to make the diagnosis and prevent debilitating joint damage 2, 3.

Several autoantibodies, including rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA), and anti-carbamylated protein antibodies, have been identified in the serum of RA patients 4. The role of these autoantibodies is critical as they may form immune complexes in the joint that contribute to the inflammatory processes that lead to articular cartilage damage. Depending on the presence or absence of RF and ACPA in RA patients’ serum, two forms of the disease have been established: Seropositive RA, which represents the most common form and is characterized by the presence of RF and or ACPA antibodies, while seronegative RA is determined by the absence of both RF and ACPA 5.

The RF test measures IgM autoantibodies that are directed against the Fc portion of IgG. Patients whose tests are positive for RF are described as being seropositive. Although about 85% of patients become seropositive at some point, this test alone is neither sufficient nor necessary to make the diagnosis 6.

Other laboratory abnormalities in rheumatoid arthritis include elevations in test results that are indicative of acute phase reactants. Such as increases in the erythrocyte sedimentation rate and C - reactive protein levels. These indicators are less specific than RF or anti-CCP antibodies, but they may help distinguish rheumatoid arthritis from non-inflammatory diseases such as osteoarthritis when physical signs are not prominent. Erythrocyte sedimentation rate and C-reactive protein level are also used to monitor therapy, unlike the RF value; these measurements do fluctuate with disease activity. Antinuclear antibodies may be detected in about 40% of patients with RA, further contributing to the complexity of the disease's laboratory profile 7.

Laboratory parameters such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and disease activity score-28 (DAS-28) are used to evaluate disease activity in RA patients. Although ESR and CRP are the most used acute phase reactants, they are non-specific, show short-term inflammation, and can be affected by many factors. In this sense, other biomarkers indicating inflammation are needed. CRP/albumin ratio (CAR) is a new laboratory indicator and CAR concentration increased in cancer and cardiovascular disease and is associated with inflammation. As a new predictive biomarker, CAR might be used to assess disease activity in RA patients, it correlates with DAS-28 in RA patients and can be used as an indicator to assess the activity of RA and give more precise results in mortality compared to CRP alone 8.

The present study was conducted to evaluate the diagnostic utility of C-reactive protein albumin ratio (CAR), acute phase reactant, calcium, and parathyroid hormone among Sudanese rheumatoid arthritis patients, and to compare the levels of RF, CRP, CAR, and Calcium between different disease activity levels (low, medium and high activity).

This case-control study included 100 cases of rheumatoid arthritis patients as study group and 100 age and sex matched healthy individual as controls. The mean value of disease duration and disease activity among cases were (8.4 ±4.6) and (4.2 ±0.821) respectively.

The mean values of RF, PTH and ESR in cases were (46.5 ± 13.8 IU/ml, 43.4 ± 21.3, pg/ml, and 28.8±12.52 mm/hr) respectively, while in controls were (5.7 ± 5.9 IU/ml, 39.8 ± 16.7 pg/ml, and 18.6 ± 6.4 mm/hr) respectively. There was significant increase in RF, PTH and ESR levels among cases compared to controls (P<0.001). Moreover, the rheumatoid patients showed significant increase in CRP (20.3 ± 7.2 mg/dl), and CAR (6.7±2.4) levels compared to controls, CRP (4.1 ± 3.4 mg/dl), and CAR (0.960 ± 0.837), (P= 0.000).

Calcium and albumin levels decreased in RA cases (6.8 ± 0.629 mg/dl and 3 ± 0.383 g/dl) respectively, compared to controls (8.8 ± 1.7 mg/dl and 4.4 ± 0.809 g/dl), (P< 0.001) as shown in Table 1 and Figure 1.

The serum calcium was not correlated with disease duration (r= -0.004, P 0.972) or disease activity (r= 0.028, P=0.779). The CAR was strongly and positively correlated with disease activity (r= 0.915, P=0.000), but not with disease duration. CRP also correlated positively with disease activity (r= 0.850, P=0.000), but not correlated with disease duration as shown in Table 2 and Figure 2 (A and B).

ROC is a plot of the sensitivity (true positive rate) at y-axis against the 1-specificity (false positive rate) at x-axis for the different possible cut-points of Albumin, CRP and CAR respectively. The area under the curve = 0.959, 0.976, and 0.984 are indicating the good accuracy of Albumin, CRP and CAR respectively, as shown in Figure 3 (A and B).

Rheumatoid arthritis (RA) is identified as the most prevalent inflammatory arthritis, significantly contributing to disability and increasing the risk of cardiovascular and pulmonary disorders 10. The present study indicated that most RA patients exhibited medium disease activity, with a higher prevalence in females, as reported in previous studies 11. İsmihan. S, et al., 2018, reported that 38% of rheumatoid patients had low disease activity or were in remission, 50.4% had moderate disease activity, and 11.6% had high disease activity 12.

The study revealed significant elevations in rheumatoid factor (RF), parathyroid hormone (PTH), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels among RA patients compared to controls. This suggests a strong inflammatory response, as these markers are known immune regulators 13. The low plasma calcium stimulates the section of parathyroid hormone so it increases according to this compensatory mechanism 9. Additionally, serum calcium and albumin levels were notably lower in RA patients, potentially due to inadequate dietary intake and the effects of chronic inflammation and steroid treatment, which can lead to osteoporosis. RA is associated with collection of chronic inflammatory cells occurring adjacent to bone with subsequent bone destruction. Furthermore, the catabolic effect of steroids treatment may contribute occasionally in liver disease, hypoalbuminemia and osteoporosis 14, 15.

A significant increase in the C-reactive protein/albumin ratio (CAR) was observed in RA patients, indicating a potential link between inflammation and CAR as a long-term biomarker for disease activity 16, 17. Some studies suggested that CAR was a long term biomarker and it would give more precise results in mortality compared to CRP alone 18, 19.

The study found a strong positive correlation between CAR and CRP levels as reported in previous work 12. Additionally, our findings suggest high predictive value of CAR in identifying RA cases. This suggests that CAR may serve as a more reliable indicator of RA and disease activity. Furthermore, the study concluded that patients with high disease activity exhibited significantly greater levels of ESR, RF, CRP, CAR, and calcium compared to those with low or medium activity, reinforcing the relationship between disease severity and inflammatory markers 12, 20.

The RF, ESR, CRP, CAR and PTH levels were significantly higher while serum calcium and albumin levels were lower among rheumatoid patients than in control. CAR was strong positively correlated with disease activity. The high CAR levels and low albumin levels were associated with the severity of RA and may be used as a good predictive biomarker for RA.