Autoantibodies in Systemic Lupus Erythematosus , on Black African Subject , in Abidjan

Aim: To determine the clinical and immunological characteristics of patients with systemic erythematosus lupus in Abidjan. Patients and Method: We studied 117 patients’ files with systemic lupus erythematosus aged 12 to 73 years old, who fulfilled the American College of Rheumatology (ACR)’s criteria. Antinuclear autoantibodies (ANA) were searched by indirect immunofluorescence. Anti-DNA native autoantibodies, extractable nuclear anti-antigens autoantibodies (anti-Sm, anti-SSA, anti-SSB and anti-RNP) and anti-phospholipids autoantibodies have been searched by ELISA technic. Results: The most frequent clinical manifestations were: articular damages (86.32%), cutaneous and mucosal lesions (71.79%) and fever (76.67%). Kidney damages have been noticed in 40.17%. Neurologic manifestations have been observed in 36.75%. Pericarditis and pleurisies have been noticed in 22.22% and 11.97% of cases, and anaemia in 86.32% of cases. ANA have been detected in 94.12% of cases, anti-DNA native’s autoantibodies in 73.53% and anti-Sm autoantibodies in 75% of cases. Anti-SS-A and anti-SS-B autoantibodies were respectively in 75% and 56.25% of cases. Anti-RNP autoantibodies were in all the patients, and anti-phospholipids autoantibodies were in 37.50% of cases. Conclusion: Systemic lupus erythematosus of Ivorian black subject is characterised by high prevalence of autoantibodies, mostly Anti-RNP.


Introduction
Systemic lupus erythematosus (SLE) is an autoimmune disease, non-specific to any organ, characterised by the production of a high variety of autoantibodies, some of which have a direct pathogenic role [1] [2].Hormonal factors, environmental and genetics factors intervened in the physiopathology [3].Clinically, SLE is characterised by its polymorphism.We have more and more data on SLE in sub-Saharan Africa [4]- [7] on black subject more specifically particular [3].Many workers from English or French speaking black Africa have reported the frequency of different clinical and biological manifestations of lupus [3]- [7].
In Ivory Coast, the study realised by Daboiko [4] in 2004 had mostly described epidemio-clinical aspects of SLE on black subject; our work is coming in addition to complete.It aims to describe autoantibodies profile in SLE on black African subject in Abidjan.

Patients and Method
It was a descriptive and retrospective study, carried out on a retrospective setup over 27 years from 1987 to December 2014 the rheumatology department's record.The following criteria were considered for the patients: should have consulted or have been hospitalized in the rheumatology department during the study period; the SLE diagnostic have been retained in front of at list 4 criteria of ACR.The patient's age at the diagnostic period matches to the age where the patient respond to ACR criteria's.For each patient, a form was design, which included clinical manifestations of the disease, blood numeration formula, sedimentation rate, C-reactive protein, and the 24 hours proteinuria.
Immunological investigations had anti-nuclear autoantibodies factors in all the cases; anti-DNA autoantibodies research and anti ENA (anti-Sm, anti-URN-P, anti SSA, anti SSB, Anti Scl 70); and anticardiolipins, rheumatoid factors, and anti-CCP.Immunological samples (ANA, Anti ENA, Anti CCP, Antiphospholipid) were all routed in France (Cerba laboratory) for analysis.
This investigation was approved by the local Ethics Committee.

Prevalence
On a sample of 18076 patients hospitalised during the study period, 117 SLE files have been found, thus a 0.64% prevalence in hospitalisation.

Age
The average age during the diagnosis was 35.76 years old, with a standard deviation of 11.956 and extremes of ages of 12 and 73 years old.The most affected age group was that of 21 -40 years (Figure 1).

Clinical Manifestations
The main clinical manifestations are illustrated on Table 1.
Articular damages constituted the most frequent clinical manifestations, because observed on 86.32% of patients.Most of the time it was arthralgia most of the time (53%).Myalgia represented 14% of cases.
An articular deformation, Jacoud's hand, was observed on 6 female patients.Fever, was the most frequent general symptom (76.07%).

Biological Characteristics
Table 2 outlines the principal biological and immunological anomalies research on this study.Anaemia was the principal haematological anomaly.Inflammatory syndrome was quasi constant (96.58% of cases).ANA were positive in 94.12% of cases with a speckled most frequently aspect (58.8%) or homogenous (26.5%).Anti-DNA native were tested positive on 73.53% of cases and anti ENA on 76.20%.
Anti-Sm was positive on 75% of cases.Antiphospholipids research was positive on 37.50% of cases.On the 26 patients who have been realised the rheumatoid factors, 14 were ended up being positives.Eight patients have realised the anti-CCP dosage, and all of them where negatives.

Limitations of the Study
The review of literature series only acted as a reference.Clinical signs have not been reported in the same conditions in all the series, the prevalence of a clinical manifestation changes according to whether it was considered at the moment of the diagnosis only; or during the patients monitoring, and the immunological tests have not been realised in the same conditions and with the same technics.In our case, the cost and accessibility of immunological tests (ANA, Anti ENA, Anti CCP, Antiphospholipid) constituted a barrier to diagnosis, immunological samples were all routed in France (Cerba laboratory) for analysis.All these factors may influence the prevalence of various signs and their variability from one series to another.As Daboiko reported [4] in his sample of 49 lupic in Abidjan, the average age and the population reported in our study, did not have particularities.The clinical predominance is classic [1]- [3], in fact the SLE is a young woman pathology [1]- [4].The average age of onset was 35.76 years old.This predominance is less pronounced at the bounding ages, this confirms the hypothesis of endocrine factors implication in the disease ethiopathogeny [1].
Our study confirms the clinical polymorphism of SLE in Abidjan and its high similitude with other regions of Africa (Table 3).
Clinical manifestations generally associated cutaneo-articular damages, kidneys, cardiovascular, pleuropulmonary and neurologic damages, with some differences according to the country studied (Table 3).In our study, articular manifestations were at the first considered, followed by general manifestations and cutaneous damages common for Cameroonian series [7], Moroccan [8] and Tunisian [9], however for Senegalese series [6] and Gabonese [5], cutaneous damages were most frequently followed by articular damages.
Articular damages inaugurate the disease in 50% of cases [1] [2].Arthralgia are frequent (53% in our series), they are often coming with myalgia.Arthritis realise habitually a bilateral and symmetric polyarthritis.Cutaneous damage's prevalence varies between 32% and 72% [10] [11].Butterfly rash, SLE characteristic has been noticed on 43.59% of cases in our series.
Neurological damages constitute the third cause of SLE mortality after infectious complications and kidney damage [2].
Neuropsychiatric manifestations have a variable frequency of 30% to 60% according to series [14] [15].It was of 36.75% in our study.
Cardiac manifestations interest the tree heart tunics with a predilection for pericardia [2].Pericarditis has been reported on 22.22% of the cases in our study.
In our countries with high tuberculosis endemicity, it is more often considered like tuberculosis and cured like it.In ours ample, interstitial pneumopathy was the most frequent of pulmonary damages.
The biological anomalies found in our sample are similar to literature data [5]- [7].An anaemia is habitual, and most often inflammatory [1]- [3] [5]- [7] [9].It reveals sometimes the SLE.Its frequency varies in literature from 8% up to 67% [2] [10] [17].It was the haematological perturbation most fre-quently seen in our study (86.32%).This high frequency of anaemia also constitutes one of the black subject particularities [3].Indeed, during compared studies of SLE realised by Petri [17] between black and white Americans subjects, it has been proved a high anaemia frequency on the black American subject.
Cameroon alone had a rate below 90% (86.1%).These high rates are the same found in American and European studies (99% on North-American [21]; 96% in European study [12] and Brazilian [22]. Detection of anti DNA native autoantibodies in our study was 73.53%.This frequency was similar to the one observed in Africa (Tunisia [9], Morocco [8], Cameroon [7]) and North America [21] and in Europe [12] but it was clearly far high than Gabonese study [5] or Senegalese [6] where Anti-DNA natives, haven't been positives on respectively 63.8% and 45.7% of cases.This can be explained by the variable sensitivity of the different research technics indeed the anti-DNA natives frequency vary from 35% up to 98% depending on series and technics used [1] [2] [10] [13] [23]- [25].
Elevated rates of anti-DNA native's autoantibodies are specific from SLE.The anti-DNA native's autoantibodies rate is correlated to a serious kidney damage existence, and to the Systemic Lupus Erythematous evolution [26].
Extractable nuclear anti-antigens autoantibodies frequency during SLE, also varies depending on the sensibility of the methods used, depending on series and sometimes depending on ethnic origin [2].
Anti-RNP was present in all our patients (100%) versus 66% in the Tunisian series [9] and 78.3% at Senegal [6].Anti-ribonucléoproteins autoantibodies (anti-RNP) can been observed on 20% to 30% of lupus, but are not specific to Systemic lupus erythematous [29].However, it has been showed a more high frequency of anti-RNP on the black African [3].Indeed, during compared studies of clinical and biological manifestations between black Africans and Caucasians living in Europe [30] or in South Africa [31], it has been found on black Africans higher frequency of anti-RNP, in addition to myalgia, seritis and kidney insufficiency.
Anti-SS-A autoantibodies have a high predictive value for SLE diagnosis among the patients tested positive on AAN, but negatives on anti-DNA native autoantibodies or Anti Sm [1] [2].Indeed, in Simmons O'Brien et al.'s study [32], he found that 47% of patients with kidney damage had anti-SS-A autoantibodies but not anti-DNA native autoantibodies.Patients with anti-SS-A autoantibodies have to be regularly followed to detect the onset of systemic manifestations [32].Anti-SSA frequency varies during SLE from 20% to 60% according to series [2] [9] [12] [13], in our study, the frequency was high (75%).
Anti-SSB autoantibodies, are particularly frequent in primitive Sjogren' syndrome (60% to 80%) while their frequency in SLE is variable according to series, to 5% up to 35% [1] [12] [13] [33].Their frequency was slightly higher (56.25%) in our study.The elevated frequency of anti SSA and SSB could also be a SLE particularity in black subjects [3].
This study shows an increase in SLE in Ivory Coast and a better knowledge of the clinical and immunological profile by the amelioration of the technical expertise and the growing augmentation of rheumatologists.

Figure 1 .
Figure 1.Distribution of SLE patients by age groups.

Table 1 .
Clinical manifestations of 117 SLE monitored in Abidjan.

Table 2 .
Biological and immunological anomalies of 117 SLE monitored in Abidjan.

Table 3 .
Compared frequency of SLE ACR criteria many series of literature.