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 Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 38  |  Issue : 1  |  Page : 23-28

Role of prolactin in activity of systemic lupus erythematosus


Dermatology Venereology and Andrology, Faculty of Medicine, Zagazig University, Zagazig, Egypt

Date of Submission14-Jul-2017
Date of Acceptance14-Nov-2017
Date of Web Publication12-Mar-2018

Correspondence Address:
Abdulla M Esawy
Dermatology Venereology and Andrology, Faculty of Medicine, Zagazig University, Zagazig, 19445
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ejdv.ejdv_32_17

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  Abstract 


Background Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease that primarily affects young women of reproductive age. The preponderance of SLE in women may result from stimulation of the immune system by female hormones. Prolactin is not only a lactogenic hormone but also an immunomodulator involved in lymphocyte survival activation and proliferation. The aim of this study is to estimate serum prolactin in SLE patients and to determine whether there is any correlation between serum PRL level and activity of SLE disease.
Subjects and methods The present study was carried out in Dermatology and Rheumatology outpatient clinics of Zagazig University hospitals. The laboratory investigations were analyzed in Clinical Pathology Department of Zagazig University. Ninety persons of both sexes participated in this study which was carried out between May 2015 and Dec 2016 on 90 subjects divided into two groups: Group A included 45 SLE patients diagnosed according to the American College of Rheumatology (ACR) classification criteria for SLE 4 of 11 criteria for definite case definition (10) and Group B included 45 apparently healthy persons who were age and sex matched and nonrelative to patients as control, SLE patients were divided according to the severity of the disease activity into 4 groups using SLEDAI.
Specific investigation Serum PRL was determined by the electrochemiluminescence immunoassay “ECLIA” by using “cobas 411” immunoassay analyzer and Elecsys prolactin II reagent kits. Normal serum PRL range was from 5–20 ng/ml.
Results In the present study, serum PRL level in SLE patients ranged from (6–27 ng/ml) with a mean PRL level ± SD of (13 ± 5.6). On the other hand, serum PRL level in the control subjects ranged from (5–20 ng/ml) with a mean PRL level ± SD of (11.8 ± 4.2). The normal range of serum PRL level is 6–20 ng/ml. No statistical significant difference were found between patients and control groups as regards serum PRL level (P > 0.05). There was increase in level of serum prolactin in severe cases of SLE followed by moderate followed by mild with statistically significant difference as P value <0.05. There was statistically significant difference, when comparing serum PRL and patients’ disease activity, as P value <0.05.
Conclusions In this study, there was no significant higher serum PRL level in SLE patients than the control group, no significant relationship between serum PRL level and SLEDAI, but a significant relation between serum PRL level and increase the severity of SLEDAI score.

Keywords: C3 & C4, prolactin, SLE


How to cite this article:
Soliman MI, Esawy AM, Khashba SA. Role of prolactin in activity of systemic lupus erythematosus. Egypt J Dermatol Venerol 2018;38:23-8

How to cite this URL:
Soliman MI, Esawy AM, Khashba SA. Role of prolactin in activity of systemic lupus erythematosus. Egypt J Dermatol Venerol [serial online] 2018 [cited 2018 Dec 14];38:23-8. Available from: http://www.ejdv.eg.net/text.asp?2018/38/1/23/227095




  Introduction Top


Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease that primarily affects young women of reproductive age, resulting from stimulation of the immune system by female hormones and hyperestrogenic state contributing to the disease process. In addition, increased serum prolactin (PRL) level plays a role in the pathogenesis and clinical expression of SLE and many other autoimmune diseases [1].

Prolactin is not only a lactogenic hormone but also an immunomodulator involved in lymphocyte survival by inhibiting glucocorticoid-induced apoptosis of lymphocytes and promoting the proliferation of B and T lymphocytes and increasing the synthesis of the cytokines interferon-γ and interleukin-2 in Th1 [2]. Prolactin receptor is a member of the hematopoietin/cytokine receptor superfamily, making it possible for PRL to play dual roles, as a cytokine and endocrinological effector [3].

PRL plays a role in maintaining immune competence by promoting the proliferation of T and B lymphocytes and natural killer cells, dendritic cell maturation, and immunoglobulin synthesis, possibly leading to the breakdown of immune tolerance [4]. PRL plays a role in the pathogenesis and clinical activity of SLE and other autoimmune diseases [5]. In animal models, hyperprolactinemia has been shown to accelerate the autoimmune process and increase mortality in lupus-prone mice [6],[7].

Increased serum PRL levels have been reported in autoimmune diseases including lupus [8]. Furthermore, suppression of PRL secretion with bromocriptine provides beneficial effects in murine lupus and perhaps in some patients with SLE as well [9]. A high level of PRL was found in patients with SLE with active disease and postpartum exacerbations [10].

The aim of this study was to estimate serum PRL in patients with SLE and to determine whether there is any correlation between serum PRL level and SLE activity.


  Patients and methods Top


Patients

The present study was carried out in Dermatology and Rheumatology Outpatient Clinics of Zagazig University hospitals. The laboratory investigations were analyzed in Clinical Pathology Department of Zagazig University. The study was carried out between May 2015 and December 2016 on 90 participants of both sexes divided into two groups: group A included 45 patients with SLE diagnosed according to the American College of Rheumatology classification criteria for SLE, satisfying at least four of 11 criteria, for definite case diagnoses [11], and group B included 45 apparently healthy persons, who were age and sex matched and were not relative of the patients, as a control group.

Exclusion criteria in both groups were pregnancy, breastfeeding, and evidence of renal, hepatic, endocrinopathic, or psychiatric disease. No concomitant medications known to affect PRL level such as α-methyldopa, reserpine, digoxin, haloperidol, or phenol thiazines were permitted during the study.

For all patients, a written informed consent was taken before inclusion in the study. The patients contributed in the study were informed about the aim of the research. Full explanation of purpose and nature of all procedures used were explained. The study was approved by the hospital’s ethics committee.

Methods

All patients were subjected to the following assessment before collecting the blood samples: history taking; general physical examination such as chest, abdominal, cardiac, ophthalmic; and full dermatological examination regarding SLE manifestations, such as malar rash, photosensitivity, oral and nasal ulcers, alopecia areata, and nonspecific rash.

Assessment of disease activity in patients with SLE was done by systemic lupus erythematosus disease activity index (SLEDAI) score: no activity 0, mild activity 1–5, moderate activity 6–10, high activity 11–19, and very high activity more than or equal to 20 [12].

Laboratory investigations

Complete blood picture, liver function tests, total protein in 24-h collected urine, erythrocyte sedimentation rate, complements C3 and C4, the presence of IgG antinuclear antibodies, and anti-ds-DNA antibodies were detected by indirect immunofluorescence.

Specific investigation

Serum PRL was determined by the electrochemiluminescence immunoassay ‘ECLIA’ by using ‘cobas 411’ immunoassay analyzer and Elecsys prolactin II reagent kits (Roche, Basel, Switzerland). Normal serum PRL range was from 5 to 20 ng/ml.

Analytical sensitivity (lower detection limit)

The detection limit represents the lowest analytic level that can be distinguished from 0. It is calculated as the value lying two SD above that of the lowest standard (master calibrator, SD: 1±2, within-run precision, normal=21). It was 1.00 µIU/ml (0.047 ng/ml).

Analytical specificity

The monoclonal antibodies used are highly specific against PRL. No cross-reaction with luteinizing hormone, follicle-stimulating hormone, thyroid-stimulating hormone, and growth hormone has been observed.

Statistical analysis

Data were checked, entered, and analyzed using SPSS version 20 (SPSS Inc., Illinois, Chicago, USA). Data were expressed as mean±SD for quantitative variables or numbers and percentage for categorical variables. χ2, t-test, analysis of variance (f-test), and correlation coefficient (r) were used when appropriate. P value less than 0.05 was considered statistically significant.


  Results Top


The current work included 90 participants. Group A included 45 patients with SLE, with 42 (93.3%) females and three (6.7%) males. Their age ranged from 18 to 53 years, with a mean±SD of 31±7.7. Group B included 45 healthy age-matched and sex-matched controls, with 25 (55.6%) females and 20 (44.4%) males. Their age ranged from 16 to 58 years with a mean±SD of 29.3±10.5, with no statistical significant difference, as P value was greater than 0.05 ([Table 1]). The clinical features of patients with SLE enrolled in this study are presented in [Table 2].
Table 1 Sex and age distribution of the studied groups

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Table 2 American College of Rheumatology criteria in patients with systemic lupus erythematosus (N=45)

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In the present study, serum PRL level in group A ranged from 6 to 27 ng/ml, with a mean PRL level±SD of 13±5.6. On the contrary, serum PRL level in group B ranged from 5 to 20 ng/ml, with a mean PRL level±SD of 11.8±4.2. No statistical significant difference were found between patients and control groups ([Table 3]) regarding serum PRL level (P>0.05).
Table 3 Prolactin level in systemic lupus erythematosus and control groups

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Patients with SLE were divided according to the severity of the disease activity into four groups using SLEDAI. There was a statistically significant difference when comparing serum PRL and patients’ disease activity, with P value of less than 0.05, as shown in [Table 4]. [Table 5] shows that there was no statistically significant correlation between PRL level and SLEDAI score in cases with SLE, as P value was greater than 0.05. However, the relation between SLEDAI score and C3 and C4 showed a statistically significantly weak negative correlation (P<0.05).
Table 4 Severity of the disease activity (systemic lupus erythematosus disease activity index) and prolactin level

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Table 5 Correlation between systemic lupus erythematosus disease activity index and C3, C4, and prolactin in cases with systemic lupus erythematosus

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  Discussion Top


PRL is a highly versatile hormone/cytokine that displays a wide spectrum of effects in a variety of tissues. In fact, more than 300 actions of PRL have been described in vertebrates. It is synthesized and secreted from specialized cells of the anterior pituitary gland, named lactotrophs, as well as from many extrapituitary tissues [13].

PRL has an immune stimulatory effect and promotes autoimmunity. PRL interferes specifically with B-cell tolerance induction and enhances proliferative response to antigens and mitogens. It also increases the production of immune globulins, cytokines, and autoantibodies. PRL has been shown to inhibit apoptosis of lymphocytes [14].

SLE is the prototypic multisystem autoimmune disorder with a broad spectrum of clinical presentations encompassing almost all organs and tissues. The extreme heterogeneity of the disease has led some investigators to propose that SLE represents a syndrome rather than a single disease. The exact pathological mechanisms of SLE remain elusive. The etiology of SLE is known to be multifactorial, involving multiple genes, sex hormones, and environmental factors including sunlight, drugs, and infections, especially involving Epstein–Barr virus [15].

The aim of this study was to estimate serum PRL in patients with SLE and to determine whether there is any correlation between serum PRL level and activity of SLE disease.

In the current study, 90 serum samples from 45 patients and 45 healthy persons were collected. Considering that factors such as age and sex could influence the PRL level and also for easy comparison of results, the controls were selected with age and sex within the same range to those of patients.

Detailed history taking and examination were done for every case before the collection of the blood sample. Exclusion of pregnant or lactating patients as well as those with renal, hepatic, endocrinopathic or psychiatric abnormalities was also done. Patients on drugs that may induce hyperprolactinemia (α-methyldopa, reserpine, verapamil, estrogen, digoxin, domperidone, and phenothiazines) were excluded as well.

Regarding this study, the sex incidence between SLE patients was as follows: 93% for females and 7% for males. Pacilio et al. [16] conducted a similar study to determine the relation between PRL and activity of SLE, and they found exactly the same sex incidence of SLE (93% for females and 6.4% for males).

Moreover, Leaños-Miranda and Cárdenas-Mondragón [17] reported nearly the same percentages of sex incidence of SLE as in the current work (93% for females and 6.1% for males).

In this work, Malar rash was the most common feature. It affected approximately 73% of patients. Photosensitivity was found in 56% of patients. Renal manifestations were found in 46.6%.

These percentages were similar to the percentages in the study of Kole and Ghosh [18] Malar rash was 80%, photosensitivity was 50%, and renal manifestations were 46.67%.

On the contrary, the percentages of remaining criteria present in our work were as follows: arthritis was 70%, hematological manifestations were 60%, and oral ulceration was found in 33.3%. Neurological manifestations were found in 10% and discoid rash affected approximately 3.3% of patients. In the study of Kole and Ghosh [18], the percentages were as follows: arthritis was 90%, hematological manifestations were 83%, oral ulceration was 56.6%, and discoid rash was 20%.

Hyperprolactinemia was found in 17% of patients with SLE (eight females) versus 0% in healthy controls. However, this showed no statistically significant difference in patients with SLE and in control group (P=3.378). In agreement with these results, Jokar et al. [19] showed in their study that hyperprolactinemia was present in 10% (9/90) for patients with SLE, with PRL level ranged from 6 to 48 ng/ml and a mean value±SD of 17.55±8.4 ng/ml. There was no statistically significant difference in patients with SLE and control group (P=0.563).

Another study showed an agreement with our study. Karimifar et al. [20], in their study, reported hyperprolactinemia was 8.4% (5/60) for patients with SLE, with a PRL level ranged from 20.3 to 24 ng/ml and a mean value±SD of 21.3±1.5 ng/ml.

Contrary to these results, Iqbal et al. [21] found that PRL level was higher in SLE than in the control group: 28.5% of patients with SLE versus 3.3% of controls had high PRL levels, with statistically significant difference in patients with SLE and in control group (P<0.05).

Moreover, another study reported contrary results. Iqbal et al. [22] found hyperprolactinemia among 35 fertile female patients having SLE in comparison with 35 control group. The mean±SD was 65.34±24.22 ng/ml among patient group and a mean±SD was 9.92±0.70 in control group, which showed statistically significant difference in patients with SLE and in control group (P<0.001).

In our work, there was no statistically significant correlation between PRL level and SLEDAI in cases with SLE, as P value was greater than 0.05 (P=0.907).

In the study by Jokar et al. [19], no statistically significant correlation between PRL level and SLEDAI score in cases with SLE was found, as P value was greater than 0.05 (P=0.343).

When Karimifar et al. [20] studied the correlation between the SLEDAI score and serum PRL level in the 60 blood samples studied, no significant correlation between PRL level and SLEDAI was found (r=0.062, P=0.39).

Against the previous results, Iqbal et al. [21] found a significant correlation between hyperprolactinemia and the SLEDAI score (P=0.004).

Moreover, Al-Bayyoumy et al. [23] found a positive significant relation between PRL level and SLEDAI score (P=0.4785, 0.0006).

This controversy about the correlation between PRL and SLE activity can be explained by the heterogeneity of the groups of patients studied, by the use of different indices to measure SLE activity, by the inclusion of patients with variable disease duration, and by the diverse methodologies used for PRL testing [16].

In our study, we found a significant statistical difference between serum PRL levels, photosensitivity, and discoid lupus like rash in our patients with high PRL level than those with normal PRL level (P<0.05). This ensures the role of PRL in exaggerating photosensitivity and DLE like rash in patients with SLE.

This was against the findings of Karimifar et al. [20] who found that there was a significant difference in the frequency of several clinical manifestations (renal involvement and hematological manifestations) and between patients with SLE with normoprolactinemia and those with hyperprolactinemia, where P values were 0.002 and 0.02, respectively.

However, the study by Jokar et al. [19] found no significant differences when the frequency of SLE clinical and serological features was compared among hyperprolactinemic and normoprolactinemic groups.

Our study and the publications that suggest that there is no alteration in pituitary PRL secretion in patients with SLE reinforce the hypothesis that the increase of PRL in some patients was because of the local production by immune cells.

Finally, in this study, there was no significant higher serum PRL level in patients with SLE than the control group, no significant relationship between serum PRL level and SLEDAI, but a significant relation between serum PRL level and increase in the severity of SLEDAI score.

The analysis of the aforementioned data suggests that chronic inflammation may affect serum PRL concentration. However, serum PRL levels are not likely to be used as a marker of the disease activity in patients with SLE.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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