Prolactin in murine systemic lupus erythematosus.

Murine systemic lupus erythematosus (SLE) manifests several autoimmune perturbations that resemble human SLE, including cytokine aberrations, lymphoproliferation, hypergammaglobulinemia, autoantibody formation, and immune complex glomerulonephritis. In multiple studies, elevated serum prolactin concentrations (hyperprolactinemia) stimulated appearance or progression of murine lupus. Autoimmune disease acceleration by prolactin appears to be accentuated by estrogen stimulation of prolactin secretion and independent of immunosuppressive effects of androgens such as testosterone. Conversely, suppression of serum prolactin concentrations by bromocriptine inhibits development of murine SLE. These data clearly support the concept that prolactin is immunostimulatory in autoimmune disease and that the therapeutic goal of lowering serum prolactin concentrations may be beneficial to patients. Further utilization of murine SLE models will facilitate dissection of the actions and interactions of prolactin with estrogen, progesterone and testosterone and lead to a better understanding of hormonal immunomodulation and therapy of autoimmune disease.     

Prolactin and macroprolactin in patients with systemic lupus erythematosus

Aim: The aim of this study was to evaluate plasma levels of prolactin and macroprolactin in a group of systemic lupus erythematosus (SLE) patients and to determine if prolactin and macroprolactin concentrations were related to disease activity, clinical features or serological abnormalities. Methods: Ninety consecutive Iranian patients with SLE were tested for serum prolactin and macroprolactin levels. Total prolactin was measured directly in serum samples by radioimmunoassay. Free prolactin was extracted from the serum using polyethylene glycol. Clinical manifestation and SLE disease activity index (SLEDAI) were recorded. Auto antibodies were determined by standard techniques. Results: There were 90 patients (7 male, 83 female) with a mean age of 27.6 ± 9.1 (range 14–52). The mean disease duration was 27.6 ± 9.1 months. The frequency of high prolactin and macroprolactin, respectively, was 10% (9/90) and 5.6% (5/90) in patients with SLE. Macroprolactinemia was found in 55.55% (5/9) of hyperprolactinemic patients. Lupus activity was present in 63.3% (57/90) of patients without a significant difference in the frequency of high serum prolactin and macroprolactin levels when compared to inactive lupus. There were no statistically significant differences regarding demographic, clinical and laboratory characteristics between the group of patients with macroprolactinemia and the group without macroprolactinemia. Conclusion: Our results suggest that a subgroup of SLE patients have hyperprolactinemia and macroprolactinemia but they do not seem to have positive or negative correlation to clinical and laboratory features and disease activity.     

Prolactin and gonadal hormones during pregnancy in systemic lupus erythematosus

We performed prospective hormonal studies in 9 patients (5 active and 4 inactive) with systemic lupus erythematosus (SLE) during pregnancy (Weeks 10 to 37). Nine healthy pregnant women and 5 patients with rheumatoid arthritis (RA) were used for comparison. Serum prolactin (PRL), testosterone and estradiol (E2) levels were determined by RIA. The patients with SLE showed higher serum PRL levels, the difference being statistically significant at Week 20, and reaching the highest levels at Weeks 30 to 40 (p = 0.05 when compared to healthy pregnant women). The 5 patients with active SLE had the highest serum PRL levels; one of these had fetal wastage. In active SLE the serum testosterone and E2 levels were decreased significantly from Weeks 10 to 30 compared with controls (p = 0.001). In patients with RA serum PRL levels, although higher than in controls, did not differ significantly, nor did the lower testosterone and E2 levels. We conclude that gonadal hormones and PRL changes observed in SLE are present also during pregnancy and may be related to fetal wastage and reactivation of disease.     

Prolactin profile in a cohort of Chinese systemic lupus erythematosus patients

Prolactin (PRL) is an important immunoregulatory hormone secreted by the anterior pituitary gland. Hyperprolactinaemia has been implicated in the pathogenesis of systemic lupus erythematosus (SLE). However, clinical studies regarding the PRL level and lupus disease activity have yielded contradictory results. The aim of our present study was, therefore, to re-evaluate the association of PRL level and disease activity in SLE by analysing a larger patient cohort and following them up serially. Seventy-two consecutive SLE patients were recruited and the serum PRL level was measured at each visit. Our results showed that hyperprolactinaemia (> 500 mIU/l) occurred in 35% (25/72) of the patients. A total of 72% (18/25) of the hyperprolactinaemic patients had mild elevation (arbitrarily defined as 500-800 mIU/l) of the level only. No correlation could be found between the PRL level and various clinical and serological parameters of lupus disease activity. On serial follow-up of 44 patients, again no correlation between PRL and disease activity could be demonstrated. We conclude that hyperprolactinaemia occurs in some patients with SLE, but the serum level of PRL does not correlate with clinical or serological disease activity and is not a reliable marker for disease monitoring. The mechanism and pathoaetiological and clinical significance of hyperprolactinaemia in a small subset of SLE patients remain unclear and a longer follow-up is necessary.      

B cell lymphokines in human systemic lupus erythematosus.

B lymphocytes of patients with systemic lupus erythematosus were studied to determine if they were intrinsically hyperresponsive to lymphokine mediators. Peripheral blood B cells from 25 lupus patients and 16 normal individuals matched for age and sex were cultured with recombinant lymphokines. B cells both from patients and normal subjects did not show increased [3H]thymidine uptake when cultured with interleukins 1, 2, and 4. The addition of Staphylococcus aureus Cowan I as costimulant increased [3H]thymidine uptake by B cells of patients and normal subjects. In the absence of T cells these recombinant lymphokines did not increase in vitro IgG or IgM production by lupus or normal B cells. Other recombinant lymphokines, interleukin 3, interferon gamma, lymphotoxin, tumour necrosis factor, and colony stimulating factors for granulocytes and macrophages were tested on lymphocytes from smaller numbers of patients and controls. Most patients in this study had inactive disease and all data suggested that B cells from patients with inactive lupus were not hyperresponsive to the lymphokines tested. In addition, the use of lymphokine gene probes for interleukins 2, 3, and 4 did not show spontaneous expression of these genes in circulating lymphocytes.     

Ascites in systemic lupus erythematosus.

Peritoneal serositis is not a widely recognised aspect of systemic lupus erythematosus (SLE). Indeed, ascites in SLE is said to occur only when complicated by the nephrotic syndrome, congestive cardiac failure, or hepatic cirrhosis. We describe two patients who developed ascites that could be attributed to none of these complications.     

Fever in systemic lupus erythematosus.

The frequency, causes, clinical and laboratory features, and outcome of febrile episodes in 160 hospitalized patients with systemic lupus erythematosus were reviewed. Eighty-three febrile episodes were identified in 63 patients and were ascribed to active lupus erythematosus alone (60 per cent), infections (23 per cent) and miscellaneous causes (17 per cent). Bacteremia was present in nine of the 19 infectious episodes and resulted in a fatal outcome in a third of the patients. Leukocytosis, neutrophilia, shaking chills and normal levels of anti-DNA antibodies were associated with infection in febrile patients with lupus erythematosus.     

ANA-negative systemic lupus erythematosus.

The presence of antinuclear antibodies (ANA) in serum is generally considered a decisive diagnostic sign of systemic lupus erythematosus (SLE). Ten patients with clinical signs of disease but persistent negative tests for ANA are examined in this study. Hair fall, Raynaud's phenomenon and recurrent oral ulcers were common in the ANA-negative group. ANA-negative SLE seems to be a subgroup of SLE that has not previously been given adequate attention.     

Update on human systemic lupus erythematosus genetics

PURPOSE OF REVIEW: Susceptibility to systemic lupus erythematosus (SLE) has a genetic component. In recent years, nine complete genome scans using family collections that differ greatly in ethnic compositions and geographic locations have identified several strong, confirmed SLE susceptibility loci. Evidence implicating individual gene polymorphisms (or haplotypes) within some of the linked intervals has been reported. This review highlights recent findings that may lead to the identification of putative genes and new insights in the pathogenesis of SLE. RECENT FINDINGS: Eight of the best-supported SLE susceptibility loci are 1q23, 1q25-31, 1q41-42, 2q35-37, 4p16-15.2, 6p11-21, 12p24, and 16q12. These are chromosomal regions exhibiting genome-wide significance for linkage in single studies and suggestive evidence for linkage in other samples. Linkage analyses conditioning on pedigrees in which one affected member manifesting a particular clinical condition have also yielded many chromosomal regions linked to SLE. The linked interval on chromosome 6p has been narrowed to 0.5 approximately 1.0 Mb (million basepairs) of 3 MHC class II containing risk haplotypes in white subjects. Cumulative results have shown that hereditary deficiencies of complement component C4A (a MHC class III gene) confer risk for SLE in almost all ethnic groups studied. The FcgammaR genes (located at 1q23) have been convincingly demonstrated to play an important role in susceptibility to SLE (and/or lupus nephritis). The evidence for the intronic single nucleotide polymorphism of program cell death gene 1 (PDCD1 at 2q37) to confer susceptibility is promising but not yet compelling. Within several established susceptibility loci, evidence for association of positional candidate genes is emerging. SUMMARY: Further replications of linkage and association are the immediate task. The respective contribution of each susceptibility gene, relationships between genotypes and phenotypes, and potential interactions between susceptibility gene products need to be elucidated. This line of investigation is now well poised to provide novel insights into how genetic variants can affect functional pathways leading to the development of SLE.     

Possible induction of systemic lupus erythematosus by human parvovirus.

A 59 year old woman presented with an influenza-like illness preceding signs and symptoms strongly suggestive of systemic lupus erythematosus (SLE), which progressed over several months. Owing to these influenza-like symptoms, a viral cause of her illness was sought. Human parvovirus B19 serology was positive and antibodies to DNA were detected by two different methods. This patient is believed to be the first report of human parvovirus B19 infection coinciding with the onset of SLE. The evidence for B19 virus and the part it plays in autoimmunity and arthritis is discussed.     

Thyroid disorders in systemic lupus erythematosus.

Of 319 patients with systemic lupus erythematosus (SLE), nine had thyrotoxicosis, three had hypothyroidism, and two had thyroiditis. This prevalence seems greater than that of similar thyroid disorders seen in the general population. It is suggested that patients with autoimmune thyroid disorders may develop SLE or vice versa. This association requires confirmation by prospective study.     

Anaplastic myeloma in systemic lupus erythematosus.

We describe a patient with systemic lupus erythematosus who developed an unusual form of anaplastic myeloma. Possible relationships between the two disease, and the role played by immunosuppressive therapy, are discussed.     

Plasma exchange in systemic lupus erythematosus.

Eight out of 10 patients studied longitudinally received benefit from plasmapheresis. The patients were used as their own controls, being treated in a steady state as far as was possible. Levels of circulating complexes did not bear a close relationship with clinical results. On the evidence plasma exchange alone does not appear to represent an important part of the long-term management of patients with systemic lupus erythematosus but may well be of value in combination with other therapy.     

Fibrinogen catabolism in systemic lupus erythematosus.

Because there is mounting evidence that localized intravascular coagulation may contribute to tissue injury following a variety of immunologic events, including immune complex diseases, fibrinogen catabolism was studied in patients with systemic lupus erythematosus to determine factors correlating with accelerated coagulation. 125I-fibrinogen half-life in controls was 90.1+/- 11 hours and the mean SLE half-life was 60.5 +/- 12. SLE patients in complete clinical remission had normal half-lives, but patients with symptomatic clinical disease, including renal disease, had significantly reduced fibrinogen survival. Accelerated fibrinogen consumption also correlated with positive tests for anti-DNA antibodies, but not with hypocomplementemia. These observations support the hypothesis that the coagulation system is activated in patients with immune complex diseases. Further studies are required to define the role, if any, that coagulation may play in causing tissue injury.