What is the clinical significance of a low titer RNP, negative Sm, but Sm/RNP that is very high titer?

Important question as I've seen clinicians incorrectly interpret anti-Sm-RNP as anti-Smith antibody.

The different autoantibodies (RNP, Smith, Sm/RNP) react to different antigens as follows:

• Anti-RNP can react to multiple components (antigens) of the U1 small nuclear RNP particle (snRNP),
• Anti-Smith reacts with a specific Smith antigen (a 14-dk protein of the snRNP),
• Anti-Sm/RNP detects antigens at the junction between the Smith antigen and the RNP antigens.

Patients can have double-positivity for anti-RNP and anti-Sm/RNP (as in your patient), isolated anti-RNP, or isolated anti-Sm/RNP antibodies.

Yours is a timely question, since Ni et al., PMID 39270208, University of Iowa, recently published a study of 133 patients with anti-Sm/RNP and/or ...