CRP in lupus
Lupus vs Infection: A physician’s Fright; CRP: A physician’s delight!
Most common causes of mortality in the first decade in lupus are infections [1]. Etiology and foci may vary but bacteria are most commonly implicated as the cause. Effect of disease and immunosuppression predisposes them to increased risk of infections. Ascertaining the cause of fever in a patient of lupus poses a great challenge. One of the dictum says lupus here, lupus there and lupus everywhere does help but infection can be a great mimicker and may co-exist and hence underscoring the importance of a good biomarker.
CRP, member of pentraxin family,recognises phosphorylcholine and carbohydrate moiety on micro-organisms and is bound by Fc receptors (FcRs) forIgG found on most phagocytes. CRP level rises significantly in lupus patients with infection [2].It rises within 6 hours and peaks by 48 hours and has a half-life of 19 hours. [3].Conventional methods can detect CRP levels above 3-10mg/l but newer methods can detect as low as 0.2 mg/l (hsCRP).
Reduced production or defective action of IL-6
Genetic differences
Table 1
Table 1 highlights the sensitivity and specificity of available markers including CRP.
| S.No | Biomarker | Cut off | Sensitivity (%) | Specificity (%) |
|---|---|---|---|---|
| 1 |
CRP
|
>6 mg/dl 1.35 mg/dl |
55 90 |
84 100 |
| 2 | Procalcitonin | >0.38 ng/ml | 74.5 | 95.5 |
| 3 | Neutrophil CD64 (nCD64) | >43.5 >2.2 |
94.4 63 |
88.9 89 |
| 4 | ESR/CRP | >15 : Lupus flare <2 : infection |
95% 100% |
|
| 5 | CRP with nCD64 | Both raised Both normal |
Probability of sepsis is 92% Rules out sepsis with 99% probability |
|
A number of studies have found CRP to be better than procalcitonin as a differentiating factor. [4]
Table 2
Limitations of most of the studies have been lack of data on viral, fungal or parasitic infections. Serositis and chronic polyarthritis also result in higher CRP though cut off has not been devised. Persistent inflammation resulting in higher IL1 and IL6 has been postulated for latter [5].Other factors affecting CRP level are shown in Table 2.
| Factors affecting CRP level | |
|---|---|
| Increased | Decreased |
| Age | Steroids |
| BMI | Anti malarial |
| Renal failure | Statins |
| OCP | |
Newer data is emerging on increase in antibodies directed against monomeric CRP (anti – mCRP) in lupus nephritis and its correlation with treatment response [6]
Clinical features and CRP,with its limitations, do serve as a good tool to differentiate lupus flare from infections. Major advantages being ease of performing the test, widespread availability, cost and a good specificity.
CRP is usually low in patients with Lupus even during times of active disease except for few situations like serositis and arthritis.
High CRP can be used as a marker for co-incident infection when the discrimination between disease activity and infection is difficult.
References
- Barber C, Gold WL, Fortin PR. Infections in the lupus patient: perspectives on prevention. Curr Opin Rheumatol2011; 23:358_65.
- Firooz N, Albert DA, Wallace DJ et al. High-sensitivityC-reactive protein and erythrocyte sedimentationrate in systemic lupus erythematosus. Lupus 2011; 20: 588_97.
- Pepys MB, Hirschfield GM. C-reactive protein: a critical update. J Clin Invest 2003; 111:1805–12.
- Kim HA, Jeon JY, An JM, Koh BR, Suh CH. C-reactive protein is a more sensitive and specific marker for diagnosing bacterial infections in systemic lupus erythematosus compared to S100A8/A9 and procalcitonin. J Rheumatol 2012; 39:728–34.
- Bywaters E G L. Jaccoud's syndrome. Clin Rheum Dis 1985; 1: 125-48.
- Katarzyna Jakuszko et al, Antibodies against monomeric C-reactive protein – A promising biomarker of lupus nephritis? Clinical Biochemistry 2017; S0009-9120(16)30373-3
Dr Pravin Hissaria, Royal Adelaide hosp, Adelaide
Dr Avinash Jain, DM resident, SGPGIMS, Lucknow
