Anti-Smith Antibodies Indicative of Poor Prognosis in Biopsy-Proven LN

The presence of anti-Smith (anti-Sm) antibodies was independently associated with early poor outcomes in biopsy-proven lupus nephritis (LN), according to a study published in the International Journal of Rheumatic Disease. 

Seven Smith proteins (B, D1, D2, D3, E, F and G) form a part of the U1, U2, U4, U5 and small ribonucleoprotein complex against which anti-Sm autoantibodies are formed. Though anti-Sm is detected in only a small portion of patients with systemic lupus erythematosus (SLE), it has a high specificity for LN. The correlation between anti-Sm positivity and renal functional status in patients with LN has not been well-defined. As such, anti-Sm testing is not routinely used to assess disease activity.  

To assess if anti-Sm antibodies were associated with poor outcomes and need for immunosuppressants in LN, Sang-Won Lee, MD, of Yonsei University College of Medicine, Seoul, South Korea, and colleagues retrospectively examined the medical records of patients with biopsy-proven LN at one hospital in South Korea.

Patients with LN eligible for inclusion into the study were diagnosed with SLE according to the American College of Rheumatology’s 1997 revised criteria, did not have history of anti-Sm testing results in the past 6 months, and who were never diagnosed with alternate medical conditions that may mimic LN, identified by International Classification of Disesases-10 codes. 

Researchers defined early poor outcomes in LN as the need for continued immunosuppresant medication more than 3 months after kidney biopsy.  Disease duration was defined as the time from diagnosis to kidney biopsy. 

“Since immunosuppressants in LN require several weeks to months for achieving maximum effect, we assumed that the administration of immunosuppressants for more than 3 months after kidney biopsy may be a surrogate for the severity of LN requiring aggressive treatment,” the authors explained.

Data analyzed included clinical, laboratory, and histological results of 149 patients with LN who had undergone biopsy. These patients had a mean age  32.0 years, median disease length 0.1 month, median follow-up duration 33.0 months, median SLE Disease Activity Index [SLEDAI] score 12.0. 

With this data, a clinical research form was generated including age, gender, disease follow-up duration, white blood cell count, platelet count, hemoglobin concentration, erythrocyte sedimentation rate, C-reaction protein, blood urea nitrogen, complement C3 and C3, lupus anticoagulant,and random urine/creatinine ratio. SLEDAI scores were also calculated. 

Serum antinuclear antibodies (ANA), including anti-Sm, anti-ribonucleoprotein (RNP), anti-Sjögren’s syndrome A (SSA)/Ro, anti-SSB/La, and anti-double stranded DNA (Anti-dsDNA) were measured via immunofluorescence.  Estimated glomerular filtration rates (eGFRs) eGFRs were calculated by the Chronic Kidney Disease Epidemiology Collaboration and the Modification of Diet in Renal Disease study equations.

Study participant baseline age (β=.961, P=.027) and SLEDAI scores (β=.206, P=.007) were significantly correlated with early poor outcomes in biopsy-proven LN.  Researchers also found that  anti-Sm positivity increased the potential of the early poor outcome of LN odds ratio [OR] 2.870, 95% confidence interval [CI], 1.033, 7.976, P= .043) after multivariate logistic regression analysis.  

Early poor outcomes were significant higher in study participants who were anti-Sm positive as compared to negative, 80.0% vs 56.5%, respectively (P=.022).

The researchers note, however, that these results may be due to the fact that anti-Sm may be participating in immune complex formation leading to renal injury.  “Thus, it could be reasonably speculated that patients with anti-Sm might require immunosuppressants in LN more frequently than those without”, the authors stated. 

Summary and Clinical Applicability

Positivity for anti-Sm antibodies identified at time of renal biopsy in patients with LN may have predictive value for early poor outcomes as defined by the need for immunnosuppressant administration (OR 2.870).

Limitations and Disclosures

This study was limited by its retrospective design, short follow-up period, and relatively small sample size kidney biopsies analyzed.   Inclusion of only patients with LN with biopsy-proven LN may have excluded patients with less severe LN.  Additionally, since anti-Sm testing is not routinely ordered during LN follow-up, the researchers were not able to assess if LN treatment would result in changes in anti-Sm.  

“Future studies that include a large number of patients will better clarify the relationship between anti-Sm with the progression and outcome of LN, which will help to determine the optimal role and meaningful period in monitoring LN,” the researchers concluded. 

Reference

Ahn, S. S., Yoo, B.-W., Song, J. J., Park, Y.-B., Lee, S.-K. and Lee, S.-W. (2016), Anti-Sm is associated with the early poor outcome of lupus nephritis. International Journal of Rheumatic Diseases. doi: 10.1111/1756-185X.12880