C-reactive protein in sarcoidosis

Sarcoidosis is characterized by granuloma formation, the macrophage being the most important building block. The activated macrophage in sarcoidosis produces interleukin-1 (II-1). It is well known that interleukin-1, among other functions, stimulates the hepatic production of C-reactive protein. We therefore prospectively measured the serum C-reactive protein in 17 patients with active pulmonary sarcoidosis, 10 patients with other chronic interstitial lung diseases of unknown etiology, 11 patients with active lung tuberculosis, and 10 healthy volunteers. Serum C-reactive protein was assayed by enzymoimmunodiffusion test. The serum C-reactive protein was negative in 13 patients suffering from active sarcoidosis and positive in four. Patients with other interstitial lung diseases had negative results in 7 and positive in 3 cases. The analyses of C-reactive protein in patients with sputum positive lung tuberculosis were positive in 10 cases. All the healthy controls had negative C-reactive protein measurements. The difference between the groups was statistically significant when sarcoidosis and tuberculosis serum C-reactive protein measurements were compared (p less than 0.01), as well as the difference between the group of other interstitial lung diseases and tuberculosis (p less than 0.01). In this respect, the measurements of serum C-reactive protein are valuable in the differentiation of sarcoidosis and other chronic interstitial lung diseases of unknown etiology from tuberculosis and other diseases which are known to induce an acute phase response.     

C-反应蛋白在动脉粥样硬化中的作用

C-反应蛋白（C-reactive protein,CRP）是反映炎症的敏感指标。近年的研究揭示超敏C-反应蛋白（high-sensitive CRP,hs-CRP）是心血管疾病的危险标志之一。同时还发现CRP自身可能直接参与了动脉继样硬化的过程,CRP可增加单核细胞向血管壁黏附、促进巨噬细胞摄取LDL,促使内皮细胞功能失调及促进平常细胞迁移和增生;CRP还与血栓形成和斑块的破裂有关。     

C-reactive protein in population samples

The significance of C-reactive protein (CRP) was studied in three different sets of specimens. Raised levels (greater than 10 mg/l) were detected in 2.0% of 380 healthy blood donors from whom two blood specimens, taken at an interval of half a year, were tested. Except for two cases, only one of the two specimens was positive. Raised levels were found three times as frequently (in 6.6%) in a random middle-aged population sample consisting of 531 subjects. More than 40% of the raised levels could be connected to acute respiratory infections, and about 20% to smoking. Five of the 35 subjects (14%) in the population sample with elevated CRP had rheumatoid arthritis. The third set of sera comprised pre-illness specimens from 22 subjects who developed rheumatoid arthritis a few months to five years later. Although it had previously been proved that the majority of these sera contained rheumatoid factors, the CRP concentration was increased in one specimen only.     

Human lymphocytes synthesize C-reactive protein

We obtained evidence for the synthesis and secretion of C-reactive protein (CRP) by peripheral mononuclear cells in culture. Human mononuclear cells isolated from peripheral blood, after depletion of platelets, were cultured in giutamine-depleted RPMI 1640 supplemented with [³H]glutamine in the presence of 10-O-tetradecanoyl-phorbol-13-acetate (TPA). Anti-CRP antiserum was added to the culture medium, and the resultant immunoprecipitate was analyzed in SDS-polyacrylamide gel electrophoresis (SDS-PAGE). The immunoprecipitate consisted of CRP, heavy and light chains of IgG, and only the CRP protein band had radioactivity, indicating that CRP was synthesized by mononuclear cells. In the populations of mononuciear cells, T-cell preparations mainly synthesized CRP, under stimulation of a factor derived from activated monocytes. Studies using the inhibitors of phospholipid metabolism suggested that generation of the monocyte factor was relevant to metabolites of an arachidonate cascade.     

C-反应蛋白与动脉粥样硬化炎症的关系

Inflammation plays a pivotal role in atherogenesis. In addition to being a potent predictive and prognostic marker for major cardiovascular events, recent evidence indicates that C-reactive protein (CRP) might directly promote atherogenesis by exerting direct effects on vascular cells. Thus, CRP will become important novel pharmaceutical targets for the treatment of atherosclerosis. This review presents an overview of the current knowledge about the pathological role of CRP in atherosclerosis initiation and progression.     

C-reactive protein and sleep-disordered breathing

STUDY OBJECTIVES: Over a 2-month period, to evaluate serum levels of C-reactive protein (CRP) in new patients with obstructive sleep apnea syndrome (OSAS), upper airway resistance syndrome (UARS), and absence of important comorbidity, as well as in normal controls. DESIGN: Cross-sectional analysis. SETTING: Sleep disorders clinic. PATIENTS: 239 successively monitored subjects: 156 subjects were diagnosed with OSAS, 39 with UARS, and 54 controls. INTERVENTIONS: none. MEASUREMENTS AND RESULTS: Clinical information (neurologic, general medical, and otolaryngology examination), body mass index, neck circumference, hip-waist ratio, Epworth Sleepiness Scale, 3 fatigue scales, Sleep Disorders Questionnaire, serum CRP, and polysomnography were collected. Analysis of variance indicated a significant difference between the groups for diastolic blood pressure, respiratory disturbance index, lowest SaO2, and body mass index. The mean serum CRP level was normal in all 3 groups. Only 15 (14 OSAS and 1 UARS) out of 239 subjects had high serum CRP values. CRP levels were significantly correlated with body mass index, esophageal pressures, hip-waist ratio, neck circumference, and blood pressure. Only body mass index was significantly associated with high CRP values; multiple regression showed: adjusted R2 = 0.115, beta = 0.345, P <.001. When men and women were considered separately, body mass index was again significantly associated with high CRP levels. CONCLUSION: Obesity is a risk factor for high serum CRP levels in patients with sleep-disordered breathing, as in the general population.     

C-reactive protein in vulnerable coronary plaques

BACKGROUND: An increased level of serum C-reactive protein (CRP) is a known prognostic factor for acute coronary events and sudden cardiac death, and it is associated with coronary calcification. CRP is expressed in coronary arteries, but its role in the development of coronary plaques is unclear. AIM: To investigate CRP immunoreactivity in relation to the severity of coronary artery disease and plaque morphology in human left anterior descending coronary arteries (LAD). METHODS: A prospective, consecutive autopsy series of 66 patients (mean age 63.4 years) in Tampere University Hospital, Tampere, Finland. RESULTS: CRP immunoreactivity was seen in 59% of the cases. In logistic regression analysis with age, sex and body mass index as confounders, CRP immunoreactivity in LAD was associated with >50% stenosis and plaque calcification. All three cases with acute coronary thrombosis due to rupture or erosion of the plaque showed a clear immunopositive reaction. CRP-positive cells were never detected in normal arteries, but were often found in early fibrous plaques (75%) and almost invariably present in the shoulder area of plaques with necrotic core (96%). CRP immunoreactivity adjacent to calcified areas in more stable plaques (71%) was less consistent with one-third of these plaques showing no immunoreactivity. CONCLUSIONS: CRP immunoreactivity is associated with the progression of atherosclerosis, and especially with unstable coronary plaques. The immunoreactivity could cease at the stable calcified stages of atherosclerosis.     

Occurrence of C-reactive protein in cryoglobulins

A previous case report described the formation of a complex between a monoclonal IgA with cryolabile properties and C-reactive protein (CRP). Our study provides the first evidence for the frequent occurrence of CRP in cryoglobulins (Cg) of all three types according to Brouet's classification. We performed a systematic immunochemical analysis of cryoglobulins from 18 patients by Western blotting and in 15 of 18 cryoprecipitates a single band (23 KD), immunoreactive with anti-CRP antibody, was demonstrable irrespective of the clonal composition of the cryoglobulins. This band was detectable in 4/5 of type I, in 6/8 of type II, and in 5/5 of type III cryoprecipitates, classified according to Brouet et al. In addition, the complement proteins C1q and C3 were present in nearly all CRP-containing cryoglobulins, presumably reflecting previous activation of the classical complement pathway at least. All three CRP-negative cryoprecipitates were derived from sera with low cryoglobulin content (1-2 g/l). Longitudinal investigation of 23 cryoprecipitates from seven patients confirmed that successful detection of CRP by Western blotting depends on the protein concentration of the cryoglobulins. Since complexed CRP was previously shown to be an effective activator of complement, via C1q binding, CRP may modulate pathophysiologic effects mediated by cryoglobulins in vivo.     

C-reactive protein in systemic lupus erythematosus

C-reactive protein (CRP) is an acute phase protein that plays a major role in the regulation of the inflammatory response. It activates the classical complement pathway in a controlled fashion, enhancing the capacity for defence against bacterial infections. It promotes the regulation of MΦ activity through FcγR, and is associated with the clearance of apo cells and nuclear antigen, thus becoming a protective molecule against pathogenic autoimmune responses in general, and systemic lupus erythematosus in particular.

CRP is also associated with atherosclerosis, both in the general population and in different auto-immune conditions. It plays a double role as a biomarker for vascular risk and as an independent risk factor as it can also perpetuate the inflammatory response.

Its multi-task behaviour makes it a pivotal structure both in the comprehension of the pathogenesis of auto-immune and inflammatory responses as well as an important tool in the clinical management of patients.     

Interference of antimodified C-reactive protein autoantibodies from lupus nephritis in the biofunctions of modified C-reactive protein

Autoantibodies against modified C-reactive protein (mCRP) are frequently found in patients with lupus nephritis and are associated with disease activity, suggesting their pathogenic role in lupus nephritis. The aim of this study was to investigate the influence of anti-mCRP autoantibodies from patients with lupus nephritis on the biofunctions of mCRP. mCRP plays important roles in the clearance of apoptotic cells and immune complex-mediated injuries via binding to C1q and factor H and acting as an opsonin. In this study, we confirmed that mCRP could bind to C1q and factor H, and the binding between mCRP and C1q was mainly via the collagen-like region of C1q by enzyme-linked immunosorbent assay and surface plasmon resonance. mCRP could significantly enhance the phagocytosis of late apoptotic cells in the presence of normal human serum. Autoantibodies against mCRP, purified from immunoglobulin G fractions of 3 patients with lupus nephritis by affinity chromatography, could significantly inhibit the binding between mCRP and C1q or factor H and reduce the clearance of late apoptotic cells enhanced by mCRP. Our observations suggest that anti-mCRP autoantibodies from patients with lupus nephritis might be pathogenic in systemic lupus erythematosus and lupus nephritis through interfering with the biofunctions of mCRP.     

C-reactive protein in acute viral infections

A sensitive solid-phase enzyme immunoassay procedure was used to determine the concentrations of C-reactive protein (CPR) in the acute and convalescent phase sera of patients with verified rubella, herpes simplex, cytomegalo, influenza A or B, enterovirus, or mycoplasma infection. In all infection groups about 90% (80% for influenza) elevated CRP values were observed in the acute phase sera (mean values in the different groups 16-57 micrograms/ml), the highest values exceeding or approaching 100 micrograms/ml. The serum CRP values were highest in all groups before the specific serum antibodies were detectable and decreased approaching the upper limit or normal controls (2 microgram/ml) within 2 weeks. Notable individual variation in the CRP production was seen. We conclude tha serum CRP determination should not be used as a reliable criterion to distinguish bacterial and viral infections.     

C-reactive protein in patients with bacteremia

Quantitative measurement of C-reactive protein (CRP) in serum has been proposed as a sensitive and, for some populations, a specific indicator of infection. To determine whether early measurement of CRP in serum could differentiate patients with bacteremia from a control group of patients whose blood cultures yielded contaminants, we measured CRP concentrations quantitatively by rate nephelometry in serum samples that had been obtained from patients on the same day as blood samples that yielded bacteria or fungi. Of the 36 episodes of bacteremia, 3 (8.5%) occurred in patients with normal concentrations of CRP in serum and 2 (5.5%) in patients with minimally elevated levels. Of the 21 episodes associated with contaminated blood cultures, only 2 (9.5%) occurred in patients with normal CRP levels. Of the patients with marked elevations of CRP (greater than 10 mg/dl), 18 (86%) had infection, although not all of these patients had bacteremia. We conclude that a normal concentration of CRP in serum does not eliminate the possibility of bacteremia. Moderate elevations (1 to 10 mg/dl) of CRP levels are common in both patients with contaminated blood cultures and in those with bacteremia. If the CRP concentration in serum is greater than 10 mg/dl and if other causes of marked elevations of CRP levels are eliminated, CRP concentration in serum may be a relatively specific indicator of infection. However, elevations of CRP concentrations are neither completely sensitive nor specific for detecting infection in patients with bacteremia.     

Polymorphism of structural forms of C-reactive protein

C-reactive protein (CRP), as a classical member of acute phase reactants, plays a variety of physiological functions in vivo and in vitro. Here we show that CRP exists in different structural forms in solution and on phospholipid membranes. At least three types of CRP structures, i.e., the pentameric ring-like form, the small globulin-like form and the fibril-like structure, were observed by combination of size-exclusion chromatography and electron microscopy. The pentameric ring-like CRPs were discovered mostly on ligand containing membrane in a calcium-dependent manner. The globulin-like monomers found on negatively charged membrane in the absence of calcium exhibited structural stability. The fibril-like structures, that have not been reported before, were formed by face-to-face stacking of pentameric CRP in a number from several to hundreds. The freshly purified CRPs form short single-strand fibrils while those CRPs stored for more than several days form long and bundled fibrils. The different structural forms may convert to each other under certain conditions, which gives some hints as to the structural basis of multiple functions of CRP.