Diagnostic utility of unidentified precipitin lines (UPLs) in immune precipitation assays

Unidentified precipitin lines (UPLs) are lines in immune precipitin assays which do not characterise with known extractable nuclear antigen (ENA) antibodies. Currently, the clinical significance of UPLs is uncertain. The aim of this study was to determine the clinical and laboratory correlates of UPLs detected over a 3 year period in a regional immunopathology laboratory. A total of 144 patients with UPLs on ENA testing were retrospectively analysed. ENA by counterimmunoelectrophoresis (CIE) was performed on 11,869 patient samples with further characterisation being performed for 1437 positive results. Ten percent of the positive ENAs demonstrated UPLs. The majority of patients with UPLs were female (71%) with an average age of 60 years. Precipitin lines for both continuously growing myeloid cell line K562 and rabbit thymus extract (RTE) were more frequent (47%), compared to K562 only (41%) or RTE only (12%). The most common antinuclear antibody (ANA) patterns associated with UPLs were speckled (29%), homogenous (16%), mixed patterns (14%), with 30% negative ANA and 5% showing cytoplasmic patterns (Golgi, GWB, mitochondrial). Both ANA positive and ANA negative patients with UPLs were generally associated with connective tissue and autoimmune disease with the majority demonstrating a positive association of UPLs with Ro52 and/or Ro60/SSA detected by Euroimmun line immunoassay. UPLs frequently seen with a negative ANA were also identified in renal disease, pulmonary fibrosis/bronchiectasis and malignancy/lymphoma. UPLs have uncertain diagnostic utility at this stage and further work needs to be done to clarify this question. UPLs were found in systemic and organ specific autoimmune disease, renal, pulmonary and neoplastic disorders. UPLs can occur in both ANA positive and ANA negative sera. The nature of the precipitating antigen in UPLs is still obscure.