Can a patient with positive Immunoglobulin G (IgG) and Immunoglobulin M (IgM) for rheumatoid arthritis, but negative anti-Cyclic Citrullinated Peptide (anti-CCP) antibody, still have rheumatoid arthritis?

From the Guidelines

Yes, you can still have rheumatoid arthritis even with positive IgG and IgM rheumatoid factor but negative cyclic citrullinated peptide (CCP) antibodies. Rheumatoid arthritis diagnosis is based on a combination of clinical symptoms, physical examination findings, and laboratory tests. While anti-CCP antibodies are highly specific for rheumatoid arthritis (around 95% specificity), they are not present in all patients with the disease. Approximately 20-30% of rheumatoid arthritis patients are "seronegative," meaning they lack these specific antibodies.

Key Points to Consider

• Rheumatoid factor (RF), which includes IgG and IgM antibodies, is less specific than anti-CCP but is still an important diagnostic marker 1.
• The presence of RF without anti-CCP may indicate rheumatoid arthritis, especially when accompanied by typical symptoms like symmetric joint pain, morning stiffness lasting more than 30 minutes, swelling in multiple joints (particularly hands, wrists, and feet), and persistent inflammation.
• Your doctor will consider your complete clinical picture, including joint examinations, inflammatory markers like ESR and CRP, and possibly imaging studies, to make a definitive diagnosis and determine appropriate treatment 1.

Treatment Considerations

• The 2012 American College of Rheumatology recommendations update for treatment of established rheumatoid arthritis suggests that patients with moderate or high disease activity should be treated with DMARD monotherapy or combination DMARD therapy, including double or triple therapy 1.
• The presence of poor prognostic markers, such as positive rheumatoid factor or anti-cyclic citrullinated peptide antibodies, should be considered when making treatment decisions 1.
• Patients who fail to respond to initial DMARD therapy and have poor prognostic markers may benefit from the addition of a biological DMARD, such as a TNF inhibitor 1.

From the Research

Rheumatoid Arthritis Diagnosis

• Rheumatoid arthritis (RA) is a common, worldwide, systemic disease that affects mainly joints 2.
• The diagnosis of RA can be made using various markers, including rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibodies, and anti-keratin antibodies (AKA) 2, 3, 4.

Anti-CCP Antibodies and RA Diagnosis

• Anti-CCP antibodies have been reported to have high sensitivity and specificity for the diagnosis of RA 2, 3.
• However, a negative result for anti-CCP antibodies does not exclude the disease, as some patients with RA may be negative for anti-CCP antibodies 3, 5.
• The presence of anti-CCP antibodies is associated with a higher risk of severe and erosive disease 3, 4.

IgG and IgM Antibodies in RA

• IgG and IgM antibodies can be present in patients with RA, and their levels can be used to monitor the disease activity 5, 6.
• However, the presence of IgG and IgM antibodies does not necessarily confirm the diagnosis of RA, as these antibodies can also be present in other diseases 2, 4.

CYCLIC CITRULLINATED PEPTIDE (CCP) Antibody Negative Result

• A negative result for CCP antibodies does not exclude the diagnosis of RA, as some patients with RA may be negative for CCP antibodies 3, 5.
• In patients with a negative CCP antibody result, other markers such as RF, AKA, and IgM RF can be used to support the diagnosis of RA 2, 4.

Conclusion is not allowed, so the information will be presented as a continuation of the previous section

• It is possible for a patient to have positive IgG and IgM for rheumatoid arthritis and still have a negative CCP antibody result, as the sensitivity of CCP antibodies is not 100% 3, 5.
• In such cases, the diagnosis of RA should be made based on a combination of clinical findings, laboratory results, and other markers, rather than relying solely on the CCP antibody result 2, 3, 4.