原文地址

https://todaysveterinarypractice.com/diagnostics/c-reactive-protein-in-dogs/

C-Reactive Protein in Dogs: A Review for the General Practitioner

犬C反应蛋白（C-Reactive Protein）：临床回顾

CRP concentration levels are emerging as a promising prognostic indicator and noninvasive tool for the management of dogs with a range of inflammatory diseases

CRP浓度水平正在成为一种有潜力的预后指标和非侵入性指标，
用于管理一系列犬的炎症性疾病。

June 16, 2023 | Issue: July/August 2023

Sydney Oberholtzer DVM 

Audrey Cook BVM&S, MSc VetEd, MRCVS, DACVIM (SAIM), DECVIM-CA, DABVP (Feline)

Abstract 摘要

C-reactive protein (CRP) is produced by the liver in response to inflammation and can be reliably measured in canine serum. Circulating concentrations of CRP increase within 24 hours of tissue injury in dogs and may be used as both a prognostic indicator (e.g., acute pancreatitis) and a management tool (e.g., immune-mediated polyarthritis, pneumonia) in routine companion animal practice.

C反应蛋白(CRP)是由肝脏对炎症反应产生的，可以在犬血清中可靠地测量。

在犬的组织损伤后24小时内，CRP血液循环浓度升高，
可作为预后指标(如急性胰腺炎)
和常规伴侣动物临床实践中的管理工具(如免疫介导的多发性关节炎、肺炎)。

This article summarizes the current understanding of CRP in canine patients and outlines specific conditions in which this novel biomarker may be diagnostically or therapeutically useful.

本文总结了目前对犬病患CRP的认识，
并概述了这种新型生物标志物可能在诊断或治疗方面有用的具体情况。

Take-Home Points

要点

• Serum concentrations of C-reactive protein (CRP) increase within 4 to 24 hours of the onset of inflammation in dogs.

• CRP measurements can be used during initial patient assessment or to determine the response to therapy.

• Specific conditions in which CRP has been investigated in dogs include immune-mediated diseases, neoplasia, pneumonia, discospondylitis, and pancreatitis.

• CRP assays are offered by veterinary reference laboratories and can be performed on in-house analyzers.

• 本文总结了目前对犬病患CRP的认识，并概述了这种新型生物标志物可能在诊断或治疗方面有用的具体情况。犬的血清C反应蛋白(CRP)浓度在炎症起始后4至24小时内升高。

• CRP测量可用于初始病患评估或确定对治疗的反应。

• 研究CRP在犬类中的具体情况包括免疫介导的疾病、肿瘤、肺炎、脊柱炎和胰腺炎。

• CRP检测由兽医参考实验室提供，并可在院内分析仪上进行。

Positive acute-phase proteins are produced by the liver in response to tissue damage and play a key role in innate responses to injury and infection. Members of this group include C-reactive protein (CRP), haptoglobin, and serum amyloid A. Of these, CRP is the most well-established. It was first identified in the 1930s in humans with pneumococcal pneumonia and is now widely regarded as a sensitive biomarker of inflammation in human patients with a range of disorders. Despite this long-standing history in human medicine, measurement of CRP has only recently gained traction in the veterinary community.

阳性急性期蛋白是由肝脏对组织损伤的反应产生的，
在对损伤和感染的先天反应中起关键作用。

这一组的成员包括
    C反应蛋白(C-reactive protein CRP)，
    触珠蛋白/结合珠蛋白（haptoglobin）
    和血清淀粉样蛋白A（serum amyloid A）。

其中，CRP是最确实已久的。

它最初于20世纪30年代在肺炎球菌肺炎病患中被发现，
现在被广泛认为是一系列疾病病患炎症的敏感生物标志物。

尽管人类医学有着悠久的历史，
但CRP的测量直到最近才在兽医界得到关注。

In healthy dogs, CRP concentrations are generally less than 20 mg/L (i.e., 20 µg/mL). However, hepatic synthesis of CRP is rapidly stimulated by interleukins 1 and 6, resulting in increased serum levels within 4 to 24 hours of infection or the onset of inflammation. Depending on the nature of the insult or injury, concentrations may increase by 10- to 1000-fold, with a peak response between 24 and 48 hours. CRP levels typically begin to decline 18 to 24 hours after the initiation of appropriate treatment or mitigation of the inciting cause.1

在健康犬中，
CRP浓度通常小于20 mg/L(即，20µg/mL)。

然而，
白细胞介素1和6可迅速刺激肝脏合成CRP，
导致感染或炎症发生后4至24小时内血清CRP水平升高。

根据病变或损伤的性质，
浓度可升高10至1000倍，
在24至48小时之间达到峰值。

C反应蛋白水平通常在开始适当治疗或缓解诱因后18至24小时开始下降。

In dogs, increases in CRP have been reported in patients with a range of conditions, including numerous infections (e.g., parvoviral enteritis, pyometra), sterile inflammatory conditions (e.g., pancreatitis), and cancers (e.g., lymphoma).2 As serum concentrations are not influenced by age, sex, or breed, this biomarker offers significant promise as an aid to the diagnosis of a wide range of diseases.

在犬，
有报道称在多种情况下，
包括
    各类感染(如细小病毒性肠炎、子宫蓄脓)、
    无菌性炎症(如胰腺炎)
    和癌症(如淋巴瘤)病患中，
CRP升高。2

由于血清浓度不受年龄、性别或品种的影响，
这种生物标志物为广泛疾病的诊断提供了重要的帮助。

When Is it Helpful to Measure CRP?

什么时候测量CRP有帮助?

In patients presenting with signs of inflammation such as pyrexia, depression, or dehydration, practitioners have traditionally relied on hematologic findings, along with serum globulin concentrations, to assess disease severity. Decreases in negative acute-phase proteins such as albumin may also be informative. However, CRP appears to be a more sensitive laboratory marker for identification and monitoring of inflammation in dogs.3 White blood cell counts, for example, may remain elevated for several days despite resolution of the underlying inflammatory condition. In addition, treatment protocols that rely on glucocorticoids may induce a persistent leukocytosis, despite effective management of the underlying disease.

在出现发热、沉郁或脱水等炎症症状的病患中，
医生传统上依靠血液学结果以及血清球蛋白浓度来评估疾病的严重程度。

阴性急性期蛋白如白蛋白的减少也可能提供信息。

然而，
CRP似乎是一种更敏感的实验室标志物，
用于识别和监测犬的炎症
例如，
尽管潜在的炎症状况得到缓解，
白细胞计数仍可能持续升高数天。

此外，
依赖糖皮质激素的治疗方案可能诱发持续的白细胞增多，
即使对潜在疾病进行了有效的管理。

Because CRP increases between 4 and 24 hours after the initiation of systemic inflammation, elevated concentrations are expected when the patient is first presented. Subsequent measurements should be performed within 18 to 24 hours of the initiation of treatment to assess response. Follow-up CRP concentrations can be measured as necessary to monitor the ongoing response to therapy.

由于CRP在全身性炎症发生后4 - 24小时内升高，
因此病患首次就诊时，
CRP浓度预计会升高。

后续测量应在治疗开始后18至24小时内进行，
以评估反应。

随访时可以测量CRP浓度，
以监测对治疗的持续反应。

What Do We Know About CRP in Dogs?

我们对犬的CRP了解多少?

CRP concentrations have been used to identify inflammation in numerous conditions, many of which are listed in BOX 1.4-17 More data are available on the usefulness of CRP in dogs with specific conditions; this information is summarized below.

C反应蛋白浓度已被用于识别多种情况下的炎症，
其中许多疾病列在方框1中。4-17

有更多关于C反应蛋白对犬特定情况下的有用性的数据;
这些信息总结如下。

BOX 1 Diseases Associated With Increased CRP Concentrations in Dogs a

方框1   与犬CRP浓度升高相关的疾病 a

• Bacterial pneumonia 4,5 细菌性肺炎

• Immune-mediated polyarthritis 6 免疫介导性多发性关节炎

• Immune-mediated hemolytic anemia 7 免疫介导性溶血性贫血

• Neoplasia 8,9 肿瘤

• Chronic enteropathy 10 慢性肠病

• Acute pancreatitis 11 急性胰腺炎

• Postsurgical trauma/infection 12,13 术后创伤/感染

• Endocarditis 14 心内膜炎

• Leptospirosis 15 钩端螺旋体病

• Congestive heart failure 14  充血性心力衰竭

• Discospondylitis 16 椎间盘脊柱炎

• Tick-borne diseases (e.g, ehrlichiosis, babesiosis, hepatozoonosis) 17 蜱媒介疾病（如，埃利希体病，巴贝斯虫病，肝簇虫病）

• Escherichia coli endotoxemia 2 大肠杆菌性内毒素血症

• Viral disease (e.g., parvovirus) 2 病毒性疾病（如，细小病毒）

CRP = C-reactive protein C-反应蛋白

a This is not an exhaustive list; other systemic inflammatory conditions also cause elevations in CRP.

a 这不是一份详尽的清单;
   还有其他全身性炎症也会导致CRP升高。

Pneumonia 肺炎

Coughing and tachypnea are common presenting complaints for canine patients in both general and emergency practices. Although radiographic findings may narrow down the list of possible causes, it can be difficult to establish a definitive diagnosis and determine the need for antibiotic therapy without invasive testing (see Case Example sidebar).

咳嗽和呼吸急促是一般临床和急诊的常见的犬病患表现主诉。

虽然X线检查结果可以缩小可能原因的范围，
但在没有侵入性检查的情况下，
很难确定明确的诊断并确定是否需要抗生素治疗(见Case Example sidebar)。

Case Example: C-Reactive Protein (CRP) Concentrations in a Dog With Pneumonia

病例: C反应蛋白(CRP)浓度的与一例犬肺炎

A 6-year-old male castrated miniature dachshund presented with acute-onset cough and lethargy. The dog had a long-standing history of aspiration pneumonia secondary to idiopathic megaesophagus. Thoracic radiographs (FIGURE 1) were consistent with aspiration pneumonia. The patient’s CRP level was greater than 60 mg/L (reference range, <10 mg/L) and he was started on oral amoxicillin/clavulanate.

一例6岁雄性已绝育的迷你腊肠犬表现为急性咳嗽和嗜睡。

该犬有长期的吸入性肺炎，继发于特发性巨食道。

胸片(图1)符合吸入性肺炎。

病患的CRP水平大于60mg/L(参考范围，10mg/L)，
开始口服阿莫西林/克拉维酸。

图1A。
就诊时的胸左侧位X线片。(A和B)
右前肺叶和右中肺叶(圈内)可见明显的肺泡型。
(A)可见充满空气的食道(箭头)。
由德州农工大学诊断影像服务提供

图1B。

就诊时胸腹背位X线片。(A和B)
右前肺叶叶和右中肺叶(圈内)可见明显的肺泡型。
由德州农工大学诊断影像服务提供

Follow-up radiographs taken 3 weeks later (FIGURE 2) showed substantial improvement; the patient was reported to be active and eating well. However, there was a persistent unstructured interstitial pulmonary pattern in the right cranial lung lobe. This was likely fibrosis secondary to prior pneumonia, but ongoing active disease could not be excluded based on radiographic findings alone. CRP was 10 mg/L at this time; antibiotics were therefore discontinued.

3周后的随访X线片(图2)显示有明显改善;
据报道，该病患活跃，饮食健康。

然而，在右前肺叶有一个持续的非结构化的间质肺型。

这可能是继发于既往肺炎的纤维化，
但仅根据影像学表现不能排除持续的活跃性疾病。

此时CRP为10 mg/L;
抗生素因此停止使用。

图2A。

抗生素治疗3周后拍摄的胸左侧位X线片。

先前所描述的分布遍及右前肺叶和右中肺叶的肺泡型的情况得到了解决。

(A)左侧位可以看到右前肺叶区域可见少量非结构化的间质型(蓝色箭头)。

整个胸内食道仍有气体适度扩张(白色箭头)。

由德州农工大学诊断影像服务提供

图2B。

抗生素治疗3周后的胸部的腹背位X线片。

先前所描述的分布遍及右前肺叶和右中肺叶的肺泡型的情况得到了解决。

由德州农工大学诊断影像服务提供

In a prospective study of 106 dogs with various respiratory diseases and 72 healthy controls, median CRP concentrations were significantly higher in dogs with bacterial pneumonia (121 mg/L) than in those with eosinophilic bronchopneumopathy (5 mg/L), chronic bronchitis (13 mg/L), pulmonary fibrosis (17 mg/L), or cardiogenic pulmonary edema (19 mg/L).18 In another study of dogs with pulmonary parenchymal disease, CRP concentrations greater than 100 mg/L were 100% specific for bacterial pneumonia (reference interval, <10 mg/L); concentrations less than 20 mg/L reliably excluded this possibility.4 However, there was no correlation between CRP concentration and disease severity in this patient population.4

在一项前瞻性研究中，
106例患有各种呼吸系统疾病的犬和72例健康的对照犬，
细菌性肺炎组的犬的中位CRP浓度(121 mg/L)
显著高于嗜酸性支气管肺炎组(5 mg/L)、慢性支气管炎组(13 mg/L)、肺纤维化组(17 mg/L)或心源性肺水肿组(19 mg/L)。

在另一项对肺实质疾病犬的研究中，
CRP浓度大于100 mg/L对细菌性肺炎的特异性为100%(参考区间为10 mg/L);
浓度低于20mg /L可以可靠地排除了这种可能性。

然而，在该病患群体中，
CRP浓度与疾病严重程度无相关性。4

In addition to guiding decisions regarding the need for antibiotic therapy, measurements of CRP may be used to determine the duration of treatment in dogs with bacterial pneumonia. Concentrations normalize with cessation of active disease, and serial measurement of CRP may be used to confirm resolution of infection. This approach appears superior to simply extending treatment for 2 weeks beyond the resolution or stabilization of radiographic abnormalities.4,19

除了指导决定是否需要抗生素治疗外，
CRP的测量还可用于确定细菌性肺炎犬的治疗时间。

随着活跃性疾病的停止，
CRP浓度恢复正常，
连续测量CRP可用于确认感染的消退。

这种方法似乎优于单纯再延长治疗超出影像学异常的消退或稳定后2周。4,19

Acute Pancreatitis

急性胰腺炎

Studies in human patients with acute pancreatitis indicate that CRP concentrations correlate with disease severity and provide useful prognostic information.20-22 In humans, severely elevated levels of CRP (>150 mg/L) have been used to help diagnose necrotizing pancreatitis.21 Therefore, the utility of CRP in dogs with acute pancreatitis has been of interest in veterinary medicine.

In a retrospective study of 22 dogs with acute pancreatitis treated at a veterinary teaching hospital, CRP measurements for the nonsurvivors (n = 7) were significantly higher than for the survivors (n = 15) on days 3 (68 mg/L versus 25.5 mg/L) and 4 (66 mg/L versus 16 mg/L) of hospitalization (reference interval, <7 mg/L). Persistently elevated CRP levels were also associated with a poorer prognosis in this population.11

A prospective study evaluated 2 clinical severity scores, CRP concentrations, and pancreatic lipase immunoreactivity in 13 dogs with acute pancreatitis. Interestingly, measurements of pancreatic lipase immunoreactivity were better correlated with clinical severity scores than CRP concentrations when all parameters were assessed on a daily basis.23 However, 10 of the 13 dogs in this study had concurrent diseases that may have affected CRP measurements. Larger studies are clearly needed to determine the clinical application of CRP in dogs with pancreatitis.

Immune-Mediated Diseases

Measurements of CRP have been reported in dogs with immune-mediated hemolytic anemia. As expected, concentrations were increased 25-fold at the time of diagnosis and decreased with appropriate treatment. Normalization (reference range, <8.9 mg/L) occurred in 7 of 10 surviving dogs within 2 weeks.24 However, there was no correlation between the magnitude of increase in CRP levels at the time of diagnosis and patient survival (nonsurvivors, 194 mg/L; survivors, 242 mg/L).24

Similarly, CRP concentrations are higher in dogs with immune-mediated polyarthropathy (IMPA). In a prospective study of 9 dogs with IMPA, CRP levels at the time of diagnosis ranged from 76.7 to 195 mg/L; this was markedly higher than for the 6 healthy controls (mean, <6.3 mg/L). CRP concentrations declined after initiation of immunosuppressive treatment and were significantly lower than baseline after 2 weeks.6 Importantly, CRP levels were correlated with synovial inflammation; an increase in CRP during or after treatment is therefore an indicator of relapse.6

Postoperative Infection

术后感染

Surgical procedures are associated with increased CRP concentrations in dogs. In 1 study, values increased 16- to 45-fold within 24 to 48 hours and were particularly elevated in patients undergoing orthopedic procedures associated with significant surgical trauma.25 However, CRP concentrations routinely normalized by the time of suture removal despite persistent elevations in white blood cell counts.25,26 These findings suggest that CRP is a more reliable indicator of postsurgical inflammation in patients undergoing orthopedic surgery than routine hematologic parameters.

外科手术与犬体内CRP浓度升高有关。

在一项研究中，
在24至48小时内，
该数值增加了16至45倍，
特别是伴有重大外科创伤的接受骨科手术的病患中。

然而，
尽管白细胞计数持续升高，
但CRP浓度在拆线时正常恢复正常。25,26

这些发现表明，
与常规血液学指标相比，
CRP是骨科手术病患术后炎症的更可靠的指标。

In bitches undergoing ovariohysterectomy for pyometra, CRP concentrations measured 4 days postoperatively were found to be higher in those with incision site infections. Affected dogs had a mean CRP concentration of 296.6 mg/L, compared with approximately 100 mg/L for the uninfected cohort.12 Measurement of CRP levels in the postoperative period may therefore provide early evidence of complications such as infection.

在因子宫蓄脓而行卵巢子宫切除术的雌性犬中，
术后4天检测的CRP浓度在有切口部位感染的雌性犬中较高。

感染犬的CRP平均浓度为296.6 mg/L，
而未感染犬的CRP平均浓度约为100 mg/L。

因此，
术后测量CRP水平可以提供诸如感染等并发症的早期证据。

Neoplasia 

肿瘤

Elevations in CRP concentrations have been reported in dogs with mammary tumors, lymphoma, mast cell tumors, sarcomas, and various metastatic neoplasias.8,9,26,27 In 60 dogs with mammary tumors, 77% of those with metastases had a CRP concentration above the upper end of the reference range.9 Elevations in CRP were also reported in dogs with benign and solitary tumors; an increased value is therefore not conclusive evidence of metastatic disease.9 The highest CRP levels seen in this study were found in dogs with ulcerated primary tumors (median, 114.4 mg/L).9 In a recent study evaluating dogs (N = 147) with CRP concentrations greater than 100 mg/L, 17 (12%) were found to have malignant neoplasia.28

据报道，
在患有乳腺肿瘤、淋巴瘤、肥大细胞瘤、肉瘤和各种转移性肿瘤的犬中，
CRP浓度升高。8,9,26,27

在60例患有乳腺肿瘤的犬中，
77%的发生转移的犬的CRP浓度高于参考范围的上限。9

在患有良性和孤立性肿瘤的犬中也报告了CRP升高;
因此， CRP增高并不能作为转移性疾病的结论性证据。

在本研究中发现，
患有溃疡 性原发性肿瘤的犬的CRP水平最高(中位数为114.4 mg/L)。9

在最近的一项研究中，
评估CRP浓度大于100 mg/L的犬(N = 147)，
发现17例(12%)患有恶性肿瘤.28

In a prospective study of dogs with mast cell tumor or sarcoma, CRP levels were significantly higher (104.1 mg/L and 262.1 mg/L, respectively) in affected dogs than in healthy controls (19.7 mg/L).8 Tumor grade did not have a significant effect on CRP concentrations.8

在一项对肥大细胞瘤或肉瘤犬的前瞻性研究中，
患病犬的CRP水平(分别为104.1 mg/L和262.1 mg/L)
显著高于健康对照组(19.7 mg/L)。8

肿瘤分级对CRP浓度无显著影响。8

Discospondylitis 

椎间盘脊柱炎

In humans with vertebral osteomyelitis, increased CRP concentrations are associated with shorter periods of preceding symptoms and higher mortality rates.29,30 In a retrospective study of dogs diagnosed with bacterial discospondylitis via magnetic resonance imaging, 11/18 (61.1%) had an elevated CRP concentration; this was >5 times the upper limit of the reference range in 10 dogs.16 In addition, this biomarker was more sensitive for the presence of infection than both fever and leukocytosis. Similar results were described in another study in which 14/16 dogs with imaging findings indicating discospondylitis had an elevated CRP concentration at the time of diagnosis (median, 100.7 mg/L).31 Back pain was present in all dogs; 12 were febrile but just 6/16 had a leukocytosis.31

在人类的椎体骨髓炎中，
CRP浓度升高与前期症状时间缩短和死亡率升高相关。29,30

在一项通过磁共振成像诊断为细菌性脊柱炎的犬的回顾性研究中，
11/18(61.1%)的CRP浓度升高;
这10例犬的CRP至少在参考范围上限的5倍以上。

此外，
该生物标志物对感染的存在，比发热和白细胞增多更敏感。

在另一项研究中也描述了类似的结果，
在诊断时，
14/16例的影像学结果显示椎间盘脊柱炎的犬的CRP浓度升高(中位数为100.7 mg/L)。

所有的犬都有背痛;
12例发热，
但仅有6/16例有白细胞增多。31

Importantly, serum CRP concentrations should be within the reference range in dogs with intervertebral disc extrusion; an elevated CRP concentration in a dog with spinal pain is therefore strongly suggestive of an inflammatory or infectious spinal condition. 27 Practitioners should bear in mind, however, that elevated CRP concentrations are also seen in patients with steroid-responsive meningitis–arteritis and is therefore not specific for discospondylitis.32

重要的是，
血清CRP浓度在椎间盘突出的犬是在参考范围内的;
因此，
脊髓疼痛犬CRP浓度升高强烈提示脊柱有炎症性或感染性疾病。

然而，
从业人员应牢记，
在类固醇反应性脊膜炎-动脉炎病患中也可见到CRP浓度升高，
因此不是椎间盘脊柱炎所特有的。

How Can We Measure CRP?

我们如何检测 CRP？

Several in-house systems offer CRP measurement for dogs; both the Catalyst CRP Test (IDEXX, idexx.com) and the Canine CRP Immunoassay (Gentian, gentian.com) have been validated for use with canine serum.33 Alternatively, samples may be submitted to major veterinary reference laboratories (e.g., Antech, Idexx), the University of Cornell Clinical Pathology Laboratory, or the Texas A&M Gastrointestinal Laboratory. Practitioners should contact the laboratory directly to verify preferred sample type and shipping requirements. This analyte is stable at 22 °C (72 °F) to 4 °C (39 °F) for 14 days33; therefore, special handling or shipment on ice is not usually necessary.

一些院内系统为犬提供CRP检测;
Catalyst CRP Test (IDEXX, idexx.com)
和Canine CRP Immunoassay (Gentian, gentian.com)
均已被证实可用于犬血清。33

或者，
样品可以提交给大型兽医参考实验室(例如，Antech, Idexx)，
康奈尔大学临床病理实验室
或德克萨斯A&M胃肠实验室。

从业者应直接与实验室联系，
确认首选样品类型和运输要求。

该分析样品在22°C(72°F)至4°C(39°F)下可以稳定14天 33;
因此，通常不需要特殊处理或冰上运输。

Results may be influenced by the specific methodology used, and reference intervals may vary between systems and laboratories. Consequently, data from different devices cannot be compared directly or used interchangeably. The same methodology should be used when assessing an individual’s response to therapy or when looking for trends.

结果可能受到所使用的具体方法的影响，
参考区间可能因系统和实验室而异。

因此，
来自不同设备的数据不能直接比较或互换使用。

在评估个体对治疗的反应或寻找趋势时，
也应该使用同样的检查方法。

Summary 总结

Biomarkers such as CRP are likely to play an increasing role in the care of companion animals, as they provide information that may not be available with routine laboratory testing. More studies are needed to better define the role of CRP as both a prognostic indicator and a noninvasive tool for the management of dogs with a range of inflammatory diseases, but the available data suggest substantial promise. Practitioners are encouraged to become familiar with the indications for measurement of CRP levels in dogs and to consider incorporating CRP measurements into patient care protocols.

C反应蛋白等生物标志物可能在照顾伴侣动物方面发挥越来越大的作用，
因为它们提供的信息可能无法通过常规实验室测试获得。

需要更多的研究来更好地定义CRP作为预后指标和治疗一系列炎症性疾病的非侵入性指标的作用，
但现有的数据显示了很大的潜力。

鼓励从业人员熟悉测量犬体内CRP水平的适应症，
并考虑将CRP测量纳入患者护理方案。

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