Research Article: Role of serum immunoglobulins for predicting sarcoidosis outcome: A cohort study

Date Published: April 11, 2018

Publisher: Public Library of Science

Author(s): Nicolas Belhomme, Stéphane Jouneau, Guillaume Bouzillé, Olivier Decaux, Mathieu Lederlin, Stéphanie Guillot, Antoinette Perlat, Patrick Jégo, Elliott D. Crouser.

http://doi.org/10.1371/journal.pone.0193122

Abstract

Sarcoidosis is a systemic granulomatous disease which carries variable outcomes. Serum protein electrophoresis is an easily accessible and routinely performed examination at diagnosis, in order to search for hypergammaglobulinemia, which is frequently found, and to rule out other granulomatous diseases such as common variable immunodeficiency. We aimed to assess the impact of baseline immunoglobulin level on the outcome of sarcoidosis.

We conducted a retrospective cohort-study, at Rennes University Hospital, in which all newly diagnosed patients for whom a serum protein electrophoresis had been performed at baseline were enrolled, from 2006 to 2014. The main outcome was the need for corticosteroid treatment within 2 years from diagnosis, the secondary outcome was the occurrence of relapse among treated patients.

Eighty patients were included in the study, and 41.25% of them exhibited an elevated globulins rate. In univariate analysis, an elevated ACE level >70 U/l, Afro-Caribbean origin, and extra-pulmonary involvement, were associated with the need for corticosteroid treatment. In multivariate analysis, only ACE elevation (OR = 1.03, IC95% 1.01–1.05, p = 0.009) and extra-pulmonary involvement (OR = 5.8, IC95% 1.4–24, p = 0.015) were significant. Immunoglobulin level was not associated with the main outcome. Regarding the secondary outcome, none of the studied features were predictive of relapse among the 34 treated patients followed for two years.

There was no relation between the immunoglobulin level at diagnosis and the evolution of sarcoidosis. An elevated ACE level and the presence of initial extra-pulmonary involvement were both associated with a more severe course of the disease necessitating a corticosteroid treatment.

Partial Text

Sarcoidosis is a systemic disease of unknown etiology, which is characterized by the development of non-necrotizing epithelioid granulomas in involved organs [1]. The course of the disease is unpredictable: spontaneous remission may occur while 20 to 70% of the patients will need a systemic therapy, for which oral corticosteroids are considered as the first-line option [1–3]. Relapse arises in 37 to 74% of treated patients [4]. Biologically, an elevated ACE is found in 60% of the patients [5]. Other parameters, such as interleukin-2 receptor, neopterin, or chitotriosidase, have been proposed for monitoring the activity of the disease, nevertheless their prognosis value needs to be confirmed, and their accessibility in routine practice is limited [6–8]. Hypergammaglobulinemia is frequently observed among sarcoidosis patients, but its relation to the disease’s course has not been established [9,10]. It has been suggested that elevated immunoglobulins or circulating immune-complex may be correlated to the disease’s course [11, 12], nonetheless no recent study has aimed to further explore this hypothesis to our knowledge [13]. As immunoglobulin level is highly influenced by many factors such as corticosteroid treatment or intercurrent infections, it is not appropriate for monitoring the disease’s activity. However, serum protein electrophoresis (SPE) is frequently performed at diagnosis, and easily accessible in routine practice. Hence, the aim of our study was to investigate the potential role of the immunoglobulin level at the time of diagnosis for predicting the disease’s course.

At the end, although the patients who required CS therapy and those who experienced a relapse had a higher baseline immunoglobulin level, our results show that such a parameter is not of interest for predicting the need for CS therapy during the first 2 years following diagnosis. Among study parameters, only ACE and extra-pulmonary involvement were found to be associated with the main outcome. In our study, 41.25% of the patients had a hypergammaglobulinemia at diagnosis, an intermediate value compared to those found in other studies [11,21]. Patients from Afro-Caribbean ethnicity had a higher rate of serum immunoglobulin compared to Caucasians (19.45 versus 12.56 g/l, p<0.001). This finding is in line with the results of Kataria and Stilzbach [11,22]. Group comparison analysis revealed that patients undergoing corticosteroid therapy had a higher immunoglobulin level than the non-treated patients (13.6 versus 12.4 g/l, p = 0.036). Treated patients who experienced a relapse had a higher rate of immunoglobulin as well (15.15 versus 12.53 g/l, p = 0.014). Multiple logistic regression showed that the serum immunoglobulin level was associated neither with disease severity as assessed by the need for CS therapy, nor with the occurrence of relapse. In multivariate analysis, extra-pulmonary involvement at diagnosis was associated with CS therapy (OR = 5.8, CI95% 1.4–24, p = 0.015). We used a stepwise selection procedure to identify the final predictors. This procedure is known to potentially fail at identifying the true predictors. However, our findings are consistent with previous studies, which showed that initial extra-pulmonary involvement entails a worsening in the disease’s course resulting in additional organs involvements [16,23]. In this cohort study including 80 patients followed for two years after sarcoidosis was diagnosed, we didn’t find an association between the immunoglobulin level at baseline and the need for CS therapy or the occurrence of relapse. Nevertheless, the patients requiring a treatment and those who experienced a relapse had a higher level of immunoglobulin, as well as Afro-Caribbean patients. The immunoglobulin level statistically improved the capacity of the model to predict relapse, bringing the need for further larger studies to confirm its potential prognosis value. Furthermore, a significant association was found between initial extra-pulmonary involvement or an elevated ACE and the need for CS therapy.   Source: http://doi.org/10.1371/journal.pone.0193122

 

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