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High sensitivity C-reactive protein (hsCRP): Association with clinical subsets in systemic lupus erythematosus (SLE) patients from Western India
i n d i a n j o u r n a l o f r h e u m a t o l o g y 8 ( 2 0 1 3 ) 6 5 e6 7
Available online at www.indianjrheumatol.com and www.sciencedirect.com
Original Article
High sensitivity C-reactive protein (hsCRP): Association with clinical subsets in systemic lupus erythematosus (SLE) patients from Western India Vandana Pradhan a,*, Anjali Rajadhyaksha b, Manisha Patwardhan a, Prathamesh Surve a, Nivedita Dhavale a, Pallavi Pandit a, Kanjaksha Ghosh a a b
Department of Clinical & Experimental Immunology, National Institute of Immunohaematology, Indian Council of Medical Research Department of Medicine, King Edward Memorial Hospital, Mumbai 400 012, Maharashtra, India
article info
abstract
Article history:
Background: High-sensitivity C-reactive protein (hsCRP) is a marker of systemic inflam-
Received 1 January 2013
mation. hsCRP have been related to disease presence and clinical activity in systemic lupus
Accepted 28 March 2013
erythematosus (SLE).
Available online 3 April 2013
Aim: To understand the association between hsCRP and SLE disease manifestations and other associated immune parameters.
Keywords:
Material & methods: One hundred and ten SLE patients were studied and SLE disease activity was
Systemic Lupus Erythematosus
evaluated by SLE Disease Activity Index (SLEDAI). Among these 42.7% patients had lupus
Lupus Nephritis
nephritis (LN). hsCRP and complement levels were detected by nephelometer.
SLE without nephritis
Results: A total of 40/110 (36.4%) had elevated hsCRP levels. High CRP was associated with
High-sensitivity C-reactive protein
presence of infection (p < 0.001) Patients having bacterial, parasitic and viral infections had
Complement levels
elevated levels of hsCRP. LN patients showed slightly higher hsCRP levels (29.3 29.9 mg/L than non-LN group (27.3 21.3 mg/L) but this difference was not significant. Patients with raised hsCRP levels showed a higher prevalence of low complement levels as compared to patients with normal CRP levels (p ¼ 0.03). Conclusion: Elevated hsCRP levels were found to be associated with infections in SLE patients and low complement levels. Elevated hsCRP levels can be used as a marker of active infection in SLE patients. Copyright ª 2013, Indian Rheumatology Association. All rights reserved.
1.
Introduction
Systemic lupus erythematosus (SLE) is characterized by systemic inflammation, and the production of a wide range of autoantibodies directed against a multiplicity of autoantigens.
Despite our growing understanding of the genetic, immunological, hormonal, and environmental factors, involved in the development of SLE, its etiology remains poorly understood. Apoptotic defects and impaired clearance of cellular and nuclear debris leads to autoantigen overload and in
* Corresponding author. Tel.: þ91 2224138518, þ91 2224138519; fax: þ91 22 24138521. E-mail address: [email protected] (V. Pradhan). 0973-3698/$ e see front matter Copyright ª 2013, Indian Rheumatology Association. All rights reserved. http://dx.doi.org/10.1016/j.injr.2013.03.007
66
i n d i a n j o u r n a l o f r h e u m a t o l o g y 8 ( 2 0 1 3 ) 6 5 e6 7
susceptible individuals, can initiate an autoimmune response. C-reactive protein (CRP) is an acute-phase protein whose concentration rises sharply during the inflammatory response. Low CRP concentration in patients with SLE may contribute to defective clearance of apoptotic particles, thereby promoting the development of autoimmunity to apoptotic vesicle components.1 High-sensitivity C-reactive protein (hsCRP) is an independent predictor of cardiovascular disease (CVD) risk but in SLE due to variability in its levels its utility as a marker of CVD is not clear.2 hsCRP has been shown to be a potential marker of CVD in secondary anti-phospholipid syndrome (APS) associated with SLE, erosive arthritis among SLE patients and subtle cognitive dysfunction in SLE.3e5 This study was designed to look at difference in the clinical features among the subset of patients with high CRP levels in SLE.
2.
Material and methods
This cross sectional study was conducted in 110 SLE patients from Rheumatology Department of KEM hospital, Mumbai, India over the period of 3 years (2008e2010). This study was carried out after obtaining ethics committee approval and a written consent from patients. SLE patients were diagnosed according to the American College of Rheumatology (ACR) criteria.6 Disease activity was assessed at the time of evaluation using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI).7 In Lupus Nephritis (LN) patients the renal histology was classified according to WHO criteria.8 Pregnant and postmenopausal women, smokers, patients with diabetes and patients with significant hyperlipemia were excluded. Clinical features as well as presence or absence of infection was recorded at the time of evaluation. After blood collection, sera were stored in aliquots at 80 C until tested. High-sensitivity CRP (hsCRP) and complement levels like C3, C4 were detected using a nephelometer (BN ProSpec, Dade Behring, Germany). The Laboratory did not have information about disease status of patients. Continuous variables are expressed as mean SD. Groups were compared using Student ‘t’ test for normally distributed data. The ‘X2’ test was used for the categorical variables. Statistical significance was set at p < 0.05.
3.
Results
A total of 110 patients with SLE (M:F ¼ 12:98) having mean age of 29 11 years and a mean disease duration of 28.9 9.9 years. Among these, 47 patients (42.7% had Lupus Nephritis (LN)). SLEDAI score among LN patients showed that 5/47 patients (10.6%) had mild disease (SLEDAI <8), 26/47 patients (55.3%) had moderate disease (SLEDAI 8e18) and 16/47 patients (34.1%) had severe disease (SLEDAI >18). Among remaining i.e. non-LN patients, 21/63 patients (33.3%) had mild disease, 36/63 patients (57.1%) had moderate disease and 6/63 patients (9.5%) had severe disease. Forty of 110 patients (36.4%) had elevated hsCRP levels (>5 mg/L). The distribution of clinical manifestations
according to ACR criteria among SLE patients with elevated and normal hsCRP levels (Table 1). High CRP was associated with presence of infection (p < 0.001). Patients having bacterial, parasitic and viral infections had elevated levels of hsCRP. LN patients showed slightly higher hsCRP levels (29.3 29.9 mg/L than non-LN group (27.3 21.3 mg/L) but this difference was not significant. It was observed that 77/110 patients (70%) had low complement levels. Patients with elevated hsCRP levels showed a higher prevalence of low complement levels as compared to patients with normal CRP levels (p < 0.05; Table 1).
4.
Discussion
Human C-reactive protein is the prototype of acute-phase proteins released during the early host response to inflammatory injury. CRP is known to mediate phagocytic responses by binding microorganisms and nuclear materials such as nucleosomes. Impairment of nuclear antigen clearance by CRP may be one way it influences the pathogenesis of SLE. CRP also affects host defense function via opsonization of pathogens. In SLE patient elevated levels of hsCRP helps to distinguish bacterial infection from active SLE. Mok et al had recently reported that hsCRP was detectable in 77% of SLE patients with clinically active disease and correlated with SLEDAI scores, particularly with serositis, musculoskeletal and hematologic system involvement. Elevated hsCRP levels in SLE were associated with certain cardiovascular risk factors and a history of arterial thromboembolism.9 Gheita et al had reported that hsCRP levels are significantly higher in anti-dsDNA positive SLE patients and hsCRP levels correlate with SLEDAI scores.10 Barner et al had reported that hsCRP levels were not associated with SLEDAI, number of ACR SLE criteria or presence of any particular organ involvement which was similar to our findings.11 Firooz et al, reported significantly higher hsCRP levels in patients with pulmonary involvement than without among SLE patients and hsCRP levels are significantly lower in SLE patients with
Table 1 e Distribution of clinical manifestations according to ACR criteria among SLE patients based on CRP levels. Clinical presentation Malar rash and/or Discoid Rash Photosensitivity Oral ulcers Arthritis Serositis Renal Disorders Neurological Disorders Hematological Disorders Myositis Alopecia Low complement levels* Infections**
Elevated CRP Normal CRP N ¼ 40 (36.4%) N ¼ 70 (63.6%) 18 (45%) 10 (25%) 13 (32.5%) 27 (67.5%) 10 (25%) 17 (42.5%) 2 (5%) 7 (17.5%) 8 (20%) 9 (22.5%) 33 (82.5%) 23 (57.5%)
*p-Value < 0.05, **p < 0.001among the two groups.
33 (47.1%) 20 (28.9%) 23 (32.9%) 43 (61.4%) 11 (15.7%) 30 (42.9%) 5 (7.1%) 9 (12.9%) 15 (21.4%) 24 (34.3%) 44 (62.9%) 11 (15.7%)
i n d i a n j o u r n a l o f r h e u m a t o l o g y 8 ( 2 0 1 3 ) 6 5 e6 7
disease flare than in those with active infection.12 Lee et al reported that hsCRP levels were associated with pulmonary and musculoskeletal features and organ damage in SLE and hsCRP may be useful to identify high-risk SLE patients.13 Rezaieyazdi et al reported that there was no correlation between hsCRP and disease activity among SLE patients from Iran but they found a positive correlation between elevated hsCRP levels and complement component individually such as C3 and C4.14 These findings were similar to our findings. SLE patients with infections were found to be significantly associated with raised hsCRP levels. Firooz et al had reported that elevated hsCRP levels can be used as a predictor of active infection in SLE patients with a high specificity.12 Though no cut-off value of CRP could be identified to distinguish SLE with infections from active lupus, nevertheless, infection needs to be ruled out in SLE patients with elevated CRP levels. The need to avoid hsCRP evaluation during times of infection or trauma and among individuals with known systemic inflammatory conditions thus may limit clinical utility. However, these effects have tended to lead to underestimation of the true predictive value of hsCRP in epidemiological studies. The utility of hsCRP testing across different ethnic groups also is uncertain. Our study supports that elevated hsCRP levels though do not directly correlate with disease activity, can be used as a predictor of active infection in SLE patients.
Conflicts of interest All authors have none to declare.
references
1. De Carvalho JF, Hanaoka B, Szyper-Kravitz M, Shoenfeld Y. Creactive protein and its implications in Systemic Lupus Erythematosus. Acta Rheumatol Port. 2007;32:317e322. 2. Nikpour M, Gladman DD, Ibanez D, Urowitz MB. Variability and correlates of high sensitivity C-reactive protein in Systemic Lupus Erythematosus. Lupus. 2009;18:966e973.
67
3. Becarevic M, Majkic-Singh N. High sensitivity C reactive protein: discriminator between patients with primary and secondary anti-phospholipid syndrome. Clin Biochem. 2008;41:1449e1453. 4. Amerzcua-Guerra LM, Marquez-Velasco R, Boialil R. Erosive arthritis in Systemic Lupus Erythematosus is associated with high serum C-reactive protein and anti-cyclic citrullinated peptide antibodies. Inflamm Res. 2008;57:555e557. 5. Shucard JL, Gaines JJ, Ambrus Jr J, Shucard DW. C-reactive protein and cognitive deficits in Systemic Lupus Erythematosus. Cogn Behav Neurol. 2007;20:31e37. 6. Hockberg MC. Updating the American College of Rheumatology revised criteria for the classification of Systemic Lupus Erythematosus. Arthritis Rheum. 1997;40:1725. 7. Bombardier C, Gladmsn FF, Urowit MB, Caron D, Chang CH. Derivation of SLEDAI: a disease activity index for lupus patients. The committee on prognosis studies in SLE. Arch Rheum. 1995;35:630e640. 8. Weening JJ, Agati VD, Schwartz MM, Seshan SV, Alpers CE, Appel GB. The classification of glomerulonephritis in Systemic Lupus Erythematosus Re visited. J Am Soc Nephrol. 2004;15:241e250. 9. Mok CC, Birmingham DJ, Ho LY, Herbert LA, Rovin BH. High sensitivity C-Reactive Protein, disease activity and cardiovascular risk factors in Systemic Lupus Erythematosus. Arthritis Care Res. 2013;65:441e447. 10. Gheita TA, El-Gazzar II , Azkalany G, El-Fishawy HS, ElFaramawy A. High sensitivity C-reactive protein (hs-CRP) in Systemic Lupus Erythematosus patients without cardiac involvement; relation to disease activity, damage and intimamedia thickness. The Egyptian Rheumatologist. 2012;34:147e152. 11. Barner E, Narain S, Naranja A, et al. High sensitivity C-reactive protein in systemic lupus erythematosus: relation to disease activity, clinical presentation and implications for cardiovascular risk. Lupus. 2005;14:576e582. 12. Firooz N, Albert DA, Wallace DJ, Ishimorim, Berel D, Weisman MH. High sensitivity and erythrocyte sedimentation rate in Systemic Lupus Erythematosus. Lupus. 2011;20:588e597. 13. Lee SS, Singh S, Link K, Petri M. High-Sensitivity C-Reactive Protein as an associate of clinical subsets and organ damage in Systemic Lupus Erythematosus. Semin Arthritis Rheum. 2008;38:41e54. 14. Rezaieyazdi Z, Sahebari M, Hatef MR, et al. Is there any correlation between high sensitive CRP and disease activity in Systemic Lupus Erythematosus. Lupus. 2011;20:1494e1500.
Available online at www.indianjrheumatol.com and www.sciencedirect.com
Original Article
High sensitivity C-reactive protein (hsCRP): Association with clinical subsets in systemic lupus erythematosus (SLE) patients from Western India Vandana Pradhan a,*, Anjali Rajadhyaksha b, Manisha Patwardhan a, Prathamesh Surve a, Nivedita Dhavale a, Pallavi Pandit a, Kanjaksha Ghosh a a b
Department of Clinical & Experimental Immunology, National Institute of Immunohaematology, Indian Council of Medical Research Department of Medicine, King Edward Memorial Hospital, Mumbai 400 012, Maharashtra, India
article info
abstract
Article history:
Background: High-sensitivity C-reactive protein (hsCRP) is a marker of systemic inflam-
Received 1 January 2013
mation. hsCRP have been related to disease presence and clinical activity in systemic lupus
Accepted 28 March 2013
erythematosus (SLE).
Available online 3 April 2013
Aim: To understand the association between hsCRP and SLE disease manifestations and other associated immune parameters.
Keywords:
Material & methods: One hundred and ten SLE patients were studied and SLE disease activity was
Systemic Lupus Erythematosus
evaluated by SLE Disease Activity Index (SLEDAI). Among these 42.7% patients had lupus
Lupus Nephritis
nephritis (LN). hsCRP and complement levels were detected by nephelometer.
SLE without nephritis
Results: A total of 40/110 (36.4%) had elevated hsCRP levels. High CRP was associated with
High-sensitivity C-reactive protein
presence of infection (p < 0.001) Patients having bacterial, parasitic and viral infections had
Complement levels
elevated levels of hsCRP. LN patients showed slightly higher hsCRP levels (29.3 29.9 mg/L than non-LN group (27.3 21.3 mg/L) but this difference was not significant. Patients with raised hsCRP levels showed a higher prevalence of low complement levels as compared to patients with normal CRP levels (p ¼ 0.03). Conclusion: Elevated hsCRP levels were found to be associated with infections in SLE patients and low complement levels. Elevated hsCRP levels can be used as a marker of active infection in SLE patients. Copyright ª 2013, Indian Rheumatology Association. All rights reserved.
1.
Introduction
Systemic lupus erythematosus (SLE) is characterized by systemic inflammation, and the production of a wide range of autoantibodies directed against a multiplicity of autoantigens.
Despite our growing understanding of the genetic, immunological, hormonal, and environmental factors, involved in the development of SLE, its etiology remains poorly understood. Apoptotic defects and impaired clearance of cellular and nuclear debris leads to autoantigen overload and in
* Corresponding author. Tel.: þ91 2224138518, þ91 2224138519; fax: þ91 22 24138521. E-mail address: [email protected] (V. Pradhan). 0973-3698/$ e see front matter Copyright ª 2013, Indian Rheumatology Association. All rights reserved. http://dx.doi.org/10.1016/j.injr.2013.03.007
66
i n d i a n j o u r n a l o f r h e u m a t o l o g y 8 ( 2 0 1 3 ) 6 5 e6 7
susceptible individuals, can initiate an autoimmune response. C-reactive protein (CRP) is an acute-phase protein whose concentration rises sharply during the inflammatory response. Low CRP concentration in patients with SLE may contribute to defective clearance of apoptotic particles, thereby promoting the development of autoimmunity to apoptotic vesicle components.1 High-sensitivity C-reactive protein (hsCRP) is an independent predictor of cardiovascular disease (CVD) risk but in SLE due to variability in its levels its utility as a marker of CVD is not clear.2 hsCRP has been shown to be a potential marker of CVD in secondary anti-phospholipid syndrome (APS) associated with SLE, erosive arthritis among SLE patients and subtle cognitive dysfunction in SLE.3e5 This study was designed to look at difference in the clinical features among the subset of patients with high CRP levels in SLE.
2.
Material and methods
This cross sectional study was conducted in 110 SLE patients from Rheumatology Department of KEM hospital, Mumbai, India over the period of 3 years (2008e2010). This study was carried out after obtaining ethics committee approval and a written consent from patients. SLE patients were diagnosed according to the American College of Rheumatology (ACR) criteria.6 Disease activity was assessed at the time of evaluation using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI).7 In Lupus Nephritis (LN) patients the renal histology was classified according to WHO criteria.8 Pregnant and postmenopausal women, smokers, patients with diabetes and patients with significant hyperlipemia were excluded. Clinical features as well as presence or absence of infection was recorded at the time of evaluation. After blood collection, sera were stored in aliquots at 80 C until tested. High-sensitivity CRP (hsCRP) and complement levels like C3, C4 were detected using a nephelometer (BN ProSpec, Dade Behring, Germany). The Laboratory did not have information about disease status of patients. Continuous variables are expressed as mean SD. Groups were compared using Student ‘t’ test for normally distributed data. The ‘X2’ test was used for the categorical variables. Statistical significance was set at p < 0.05.
3.
Results
A total of 110 patients with SLE (M:F ¼ 12:98) having mean age of 29 11 years and a mean disease duration of 28.9 9.9 years. Among these, 47 patients (42.7% had Lupus Nephritis (LN)). SLEDAI score among LN patients showed that 5/47 patients (10.6%) had mild disease (SLEDAI <8), 26/47 patients (55.3%) had moderate disease (SLEDAI 8e18) and 16/47 patients (34.1%) had severe disease (SLEDAI >18). Among remaining i.e. non-LN patients, 21/63 patients (33.3%) had mild disease, 36/63 patients (57.1%) had moderate disease and 6/63 patients (9.5%) had severe disease. Forty of 110 patients (36.4%) had elevated hsCRP levels (>5 mg/L). The distribution of clinical manifestations
according to ACR criteria among SLE patients with elevated and normal hsCRP levels (Table 1). High CRP was associated with presence of infection (p < 0.001). Patients having bacterial, parasitic and viral infections had elevated levels of hsCRP. LN patients showed slightly higher hsCRP levels (29.3 29.9 mg/L than non-LN group (27.3 21.3 mg/L) but this difference was not significant. It was observed that 77/110 patients (70%) had low complement levels. Patients with elevated hsCRP levels showed a higher prevalence of low complement levels as compared to patients with normal CRP levels (p < 0.05; Table 1).
4.
Discussion
Human C-reactive protein is the prototype of acute-phase proteins released during the early host response to inflammatory injury. CRP is known to mediate phagocytic responses by binding microorganisms and nuclear materials such as nucleosomes. Impairment of nuclear antigen clearance by CRP may be one way it influences the pathogenesis of SLE. CRP also affects host defense function via opsonization of pathogens. In SLE patient elevated levels of hsCRP helps to distinguish bacterial infection from active SLE. Mok et al had recently reported that hsCRP was detectable in 77% of SLE patients with clinically active disease and correlated with SLEDAI scores, particularly with serositis, musculoskeletal and hematologic system involvement. Elevated hsCRP levels in SLE were associated with certain cardiovascular risk factors and a history of arterial thromboembolism.9 Gheita et al had reported that hsCRP levels are significantly higher in anti-dsDNA positive SLE patients and hsCRP levels correlate with SLEDAI scores.10 Barner et al had reported that hsCRP levels were not associated with SLEDAI, number of ACR SLE criteria or presence of any particular organ involvement which was similar to our findings.11 Firooz et al, reported significantly higher hsCRP levels in patients with pulmonary involvement than without among SLE patients and hsCRP levels are significantly lower in SLE patients with
Table 1 e Distribution of clinical manifestations according to ACR criteria among SLE patients based on CRP levels. Clinical presentation Malar rash and/or Discoid Rash Photosensitivity Oral ulcers Arthritis Serositis Renal Disorders Neurological Disorders Hematological Disorders Myositis Alopecia Low complement levels* Infections**
Elevated CRP Normal CRP N ¼ 40 (36.4%) N ¼ 70 (63.6%) 18 (45%) 10 (25%) 13 (32.5%) 27 (67.5%) 10 (25%) 17 (42.5%) 2 (5%) 7 (17.5%) 8 (20%) 9 (22.5%) 33 (82.5%) 23 (57.5%)
*p-Value < 0.05, **p < 0.001among the two groups.
33 (47.1%) 20 (28.9%) 23 (32.9%) 43 (61.4%) 11 (15.7%) 30 (42.9%) 5 (7.1%) 9 (12.9%) 15 (21.4%) 24 (34.3%) 44 (62.9%) 11 (15.7%)
i n d i a n j o u r n a l o f r h e u m a t o l o g y 8 ( 2 0 1 3 ) 6 5 e6 7
disease flare than in those with active infection.12 Lee et al reported that hsCRP levels were associated with pulmonary and musculoskeletal features and organ damage in SLE and hsCRP may be useful to identify high-risk SLE patients.13 Rezaieyazdi et al reported that there was no correlation between hsCRP and disease activity among SLE patients from Iran but they found a positive correlation between elevated hsCRP levels and complement component individually such as C3 and C4.14 These findings were similar to our findings. SLE patients with infections were found to be significantly associated with raised hsCRP levels. Firooz et al had reported that elevated hsCRP levels can be used as a predictor of active infection in SLE patients with a high specificity.12 Though no cut-off value of CRP could be identified to distinguish SLE with infections from active lupus, nevertheless, infection needs to be ruled out in SLE patients with elevated CRP levels. The need to avoid hsCRP evaluation during times of infection or trauma and among individuals with known systemic inflammatory conditions thus may limit clinical utility. However, these effects have tended to lead to underestimation of the true predictive value of hsCRP in epidemiological studies. The utility of hsCRP testing across different ethnic groups also is uncertain. Our study supports that elevated hsCRP levels though do not directly correlate with disease activity, can be used as a predictor of active infection in SLE patients.
Conflicts of interest All authors have none to declare.
references
1. De Carvalho JF, Hanaoka B, Szyper-Kravitz M, Shoenfeld Y. Creactive protein and its implications in Systemic Lupus Erythematosus. Acta Rheumatol Port. 2007;32:317e322. 2. Nikpour M, Gladman DD, Ibanez D, Urowitz MB. Variability and correlates of high sensitivity C-reactive protein in Systemic Lupus Erythematosus. Lupus. 2009;18:966e973.
67
3. Becarevic M, Majkic-Singh N. High sensitivity C reactive protein: discriminator between patients with primary and secondary anti-phospholipid syndrome. Clin Biochem. 2008;41:1449e1453. 4. Amerzcua-Guerra LM, Marquez-Velasco R, Boialil R. Erosive arthritis in Systemic Lupus Erythematosus is associated with high serum C-reactive protein and anti-cyclic citrullinated peptide antibodies. Inflamm Res. 2008;57:555e557. 5. Shucard JL, Gaines JJ, Ambrus Jr J, Shucard DW. C-reactive protein and cognitive deficits in Systemic Lupus Erythematosus. Cogn Behav Neurol. 2007;20:31e37. 6. Hockberg MC. Updating the American College of Rheumatology revised criteria for the classification of Systemic Lupus Erythematosus. Arthritis Rheum. 1997;40:1725. 7. Bombardier C, Gladmsn FF, Urowit MB, Caron D, Chang CH. Derivation of SLEDAI: a disease activity index for lupus patients. The committee on prognosis studies in SLE. Arch Rheum. 1995;35:630e640. 8. Weening JJ, Agati VD, Schwartz MM, Seshan SV, Alpers CE, Appel GB. The classification of glomerulonephritis in Systemic Lupus Erythematosus Re visited. J Am Soc Nephrol. 2004;15:241e250. 9. Mok CC, Birmingham DJ, Ho LY, Herbert LA, Rovin BH. High sensitivity C-Reactive Protein, disease activity and cardiovascular risk factors in Systemic Lupus Erythematosus. Arthritis Care Res. 2013;65:441e447. 10. Gheita TA, El-Gazzar II , Azkalany G, El-Fishawy HS, ElFaramawy A. High sensitivity C-reactive protein (hs-CRP) in Systemic Lupus Erythematosus patients without cardiac involvement; relation to disease activity, damage and intimamedia thickness. The Egyptian Rheumatologist. 2012;34:147e152. 11. Barner E, Narain S, Naranja A, et al. High sensitivity C-reactive protein in systemic lupus erythematosus: relation to disease activity, clinical presentation and implications for cardiovascular risk. Lupus. 2005;14:576e582. 12. Firooz N, Albert DA, Wallace DJ, Ishimorim, Berel D, Weisman MH. High sensitivity and erythrocyte sedimentation rate in Systemic Lupus Erythematosus. Lupus. 2011;20:588e597. 13. Lee SS, Singh S, Link K, Petri M. High-Sensitivity C-Reactive Protein as an associate of clinical subsets and organ damage in Systemic Lupus Erythematosus. Semin Arthritis Rheum. 2008;38:41e54. 14. Rezaieyazdi Z, Sahebari M, Hatef MR, et al. Is there any correlation between high sensitive CRP and disease activity in Systemic Lupus Erythematosus. Lupus. 2011;20:1494e1500.