Two EPS proteins are diagnostic markers for CPPS

November 1, 2005

Chicago--A study of cytokines in expressed prostatic secretions (EPS) has identified two potential candidates as diagnostic markers for inflammatory and noninflammatory forms of chronic prostatitis/chronic pelvic pain syndrome (CPPS), according to researchers from Northwestern University Medical Center in Chicago.

Chicago-A study of cytokines in expressed prostatic secretions (EPS) has identified two potential candidates as diagnostic markers for inflammatory and noninflammatory forms of chronic prostatitis/chronic pelvic pain syndrome (CPPS), according to researchers from Northwestern University Medical Center in Chicago.

Macrophage inflammatory protein 1-alpha (MIP-1α) and monocyte chemoattractant protein-1 (MCP-1) were significantly elevated in patients with CPPS compared with a control group of men without CPPS. Elevation of the cytokines in noninflammatory CPPS is a novel finding that might represent evidence of a biological basis for the condition.

"The key thing is that, in the past, people have said that the [noninflammatory CPPS] patients may have psychological issues and that there's no objective marker for the disease process except for the fact that the patients have symptoms," said lead study author Jeffrey Stern, MD, chief urology resident at Northwestern, working with Anthony J. Schaeffer, MD.

The study, presented at the AUA annual meeting in San Antonio, was a continuation of ongoing work aimed at identifying potential markers for CPPS in EPS. Dr. Stern and his colleagues previously demonstrated elevated levels of the cytokines interleukin-1β (IL-1β), tumor necrosis factor-alpha, IL-8, and neutrophil-activating peptide-78 in men with CPPS IIIa.

In an effort to identify objective parameters of inflammation associated with CPPS, MIP-1a and MCP-1 were measured in the EPS of healthy men and in those with CPPS. MIP-1a has chemotactic activity for macrophages and T-lymphocytes, and the cytokine has been shown to be elevated in the serum and synovial fluid of patients with rheumatoid arthritis.

MCP-1 has specific chemotactic and activating activity for monocytes. The cytokine has been found in human abdominal aortic aneurysms, in elevated levels in serum and synovial fluid of rheumatoid arthritis patients, and in lesions from patients with Peyronie's disease.

The current study involved a total of 89 men: 13 healthy volunteers, 32 patients with inflammatory CPPS (NIH category IIIa), and 44 patients with noninflammatory CPPS (IIIb). Enzyme-linked immunosorbent assays of EPS were performed for MIP-1a in all 89 men and for MCP-1 in 72 men. Investigators performed receiver operator characteristics (ROC) analysis to determine whether cutoff points could be established to differentiate between CPPS patients and controls.

Protein degree is key

MIP-1α and MCP-1 were detected in all patients; however, both cytokines were significantly elevated in patients with inflammatory and noninflammatory CPPS compared with the control group, Dr. Stern said.

Mean levels of MIP-1α were 140.07 pg/mL for controls, 1,057.75 pg/mL for patients with inflammatory CPPS, and 978.37 pg/mL for men with noninflammatory CPPS (p=.0003). The control group had a mean MCP-1 level of 599.43 pg/mL compared with 3261.20 pg/mL for inflammatory CPPS and 2,271.67 pg/mL for noninflammatory CPPS (p=.0002).

Using a cutoff of 146 pg/mL as a positive test for MIP-1a, 55 of 76 CPPS patients exceeded that level, compared with four of 13 men in the control group. The test had a sensitivity of 72.4% and a specificity of 69.2%, and the area under the ROC curve was 0.810. For MCP-1, a cutoff of 704 pg/mL was exceeded by 52 of 62 CPPS patients compared with one of 10 controls, resulting in a sensitivity of 83.9%, a specificity of 90%, and area under the ROC curve of 0.856.

Combining the cutoff points for MIP-1a and MCP-1 resulted in a sensitivity of 88.7%, a specificity of 80.0%, and an area under the ROC curve of 0.892.

"Unlike previous studies where cytokine levels were found to be elevated only in inflammatory CPPS, we have demonstrated elevated levels of MIP-1α and MCP-1 in noninflammatory CPPS as well," Dr. Stern and colleagues concluded. "MIP-1a and MCP-1 may prove to be biomarkers for both inflammatory and noninflammatory CPPS."