Antiprolactin autoantibodies in systemic lupus erythematosus: frequency and correlation with prolactinemia and disease activity.

OBJECTIVE: To determine in patients with systemic lupus erythematosus (SLE) (1) the frequency of antiprolactin (anti-PRL) autoantibodies, and (2) the relationships among anti-PRL autoantibodies, serum prolactin (PRL) levels, and lupus activity. METHODS: In a cross sectional study 259 consecutive patients with SLE were tested for serum PRL levels and anti-PRL autoantibodies based on disease activity. RESULTS: The frequency of anti-PRL was 5% (13/259), and all SLE patients with anti-PRL had hyperprolactinemia. There was lupus activity in 110 patients (42.5%) and there was no significant difference in frequency of anti-PRL autoantibodies between patients with or without lupus activity (5.5 vs 4.7%; p = 0.99). Only a high level of serum PRL was associated with lupus activity independent from other studied variables (p = 0.024). There was a negative but nonsignificant correlation between the titers of anti-PRL autoantibody and SLEDAI (r(s) = -0.16, p = 0.59). Anti-PRL positive patients had higher levels of serum PRL than anti-PRL negative patients (33.2+/-13.8 vs 11.6+/-13.2 ng/ml; p = 0.0001) and a significantly different frequency of hyperprolactinemia (100 vs 11.4%; p = 0.00001). CONCLUSION: The presence of anti-PRL autoantibodies was associated with hyperprolactinemic status and high serum PRL levels; these data suggest that anti-PRL autoantibodies could be the cause of hyperprolactinemia in a subset of patients with SLE. An increase in serum PRL levels proved to be an important independent factor related to lupus activity, but there was no relationship between anti-PRL autoantibodies and lupus activity.

Detection of macroprolactinemia with the polyethylene glycol precipitation test in systemic lupus erythematosus patients with hyperprolactinemia.

The objective of this study was to determine the diagnostic performance of the percentage of serum prolactin (PRL) precipitated with polyethylene glycol (PEG) for the detection of macroprolactinemia in systemic lupus erythematosus (SLE) patients with hyperprolactinemia. Serum samples from SLE patients were examined. Serum PRL was measured by immunoradiometric assay (IRMA) and samples with hyperprolactinemia (> 20 ng/ml) were submitted to PEG precipitation, gel filtration chromatography and affinity chromatography with protein-G sepharose. A comparative survey was used. Among 259 consecutive serum samples from SLE patients, PRL was > 20.1 ng/ml in 43 samples (16.6%). Gel filtration showed a predominant pattern of macroprolactinemia (> 100 kDa) in 14 (32.6%), a predominant pattern of monomeric PRL (23 kDa) in 27 (62.7%), and a variable pattern in two (4.7%). All sera with a predominant pattern of macroprolactinemia displayed anti-PRL autoantibodies by affinity chromatography for IgG. The best cut-off point for percentage of serum PRL precipitated with PEG for detection of macroprolactinemia was > or = 58.4%. Sensitivity and specificity were 100 and 96.6%, respectively. We can conclude that PEG precipitation is a convenient and simple procedure to screen for the presence of macroprolactinemia in sera from SLE patients. Precipitations > or = 58.4% are indicative of the presence of, and those < 50% the absence of, macroprolactinemia. However, samples with precipitations between 50 and 58.3% require gel filtration chromatography to characterize the predominant molecular form of PRL. Therefore, it is important to take these findings into account in future studies that aim to establish a relationship between PRL and disease activity in SLE.

Persistence of macroprolactinemia due to antiprolactin autoantibody before, during, and after pregnancy in a woman with systemic lupus erythematosus.

A woman with systemic lupus erythematosus (SLE) with marked increases in circulating 150-kDa PRL was studied from before conception, throughout pregnancy, and after pregnancy. The clinical features of the patient included idiopathic hyperprolactinemia without clinical symptoms such as amenorrhea and galactorrhea before pregnancy. No clinical lupus activity was present during follow-up. Serum PRL increase during pregnancy in this patient was considerably higher at weeks 27 and 33 than in normal pregnant women. In contrast, serum-free PRL levels were considerably lower at weeks 20, 27, and 33 than in normal pregnant women. A 150-kDa PRL (big big PRL) species persisted as the predominant circulating form of PRL throughout each measurement in this woman with SLE. In contrast, the predominant form of PRL in serum from healthy pregnant women was little PRL (or monomeric PRL). The nature of big big PRL was due to the presence of anti-PRL autoantibodies forming an IgG-23 kDa PRL complex, in accordance with the studies by affinity chromatography for IgG and Western blot analysis. The IgG-PRL complex was fully bioactive in vitro (Nb2 rat lymphoma cell assay). Injection of the serum into the rats demonstrated that the IgG-PRL complex was cleared more slowly than serum containing predominantly monomeric PRL. The data suggest that the IgG-PRL complex has biological activity; the absence of symptoms in this woman may be attributed to the fact that due to its large molecular weight, big big PRL does not easily cross the capillary walls. Delayed clearance may account for increased serum PRL levels in this SLE patient with anti-PRL autoantibodies.

Frequency of macroprolactinemia due to autoantibodies against prolactin in pregnant women.

The frequency of macroprolactinemia related to the presence of anti-PRL autoantibodies in the serum of 209 healthy women at different stages of pregnancy was studied. Measurements were taken of serum PRL concentrations before and after chromatographic separation (gel filtration and affinity with proteins A and G) and extraction of free PRL with polyethylene glycol (PEG). Sera from 8 of the 209 women (3.8%) were found to have a significantly high proportion of precipitated PRL by PEG (macroprolactinemia); in these patients, gel filtration showed that a substantial amount of big big PRL (molecular mass >100 kDa) was present (19.0--78.2% vs. 3.8-4.9%, P = 0.009 in normal pregnant women with a normal proportion of precipitated PRL by PEG). The presence of macroprolactinemia was attributable to anti-PRL autoantibodies in 5 of the 8 women. Comparison of serum levels of direct and free PRL between women with macroprolactinemia related to anti-PRL autoantibodies and women without macroprolactinemia showed significant differences (direct PRL: 270.2 +/- 86.9 vs. 203.4 +/- 69.0 microg/L, P = 0.04; and free PRL: 107.0 +/- 75.9 vs. 173.3 +/- 67.6 microg/L, P = 0.002). On the other hand, there was no difference between women with macroprolactinemia not related to anti-PRL autoantibodies and women with macroprolactinemia caused by anti-PRL autoantibodies, nor was there a difference between women with macroprolactinemia not related to anti-PRL autoantibodies and women without macroprolactinemia. There was a positive correlation between titers of the anti-PRL autoantibody and serum PRL levels (r = 0.82, P = 0.09). The presence of the anti-PRL autoantibody had no relation to the patient's age, stage of gestation, or number of previous pregnancies. We concluded that the frequency of macroprolactinemia was 3.8% among healthy, pregnant women, which was caused by a anti-PRL autoantibodies in 62.5% of the cases. The autoantibodies were found in the bloodstream, forming a PRL-IgG complex, in accordance with the following observations: 1) immunoreactive PRL on gel filtration was eluted in the fractions corresponding to the molecular mass of IgG (150 kDa); 2) a significantly high proportion of immunoreactive PRL was retained on an affinity gel for IgG (proteins A and G); and 3) a significantly high proportion of serum PRL bound to IgG was precipitated by protein A. There was a positive correlation between titers of anti-PRL autoantibodies and serum PRL levels. Serum levels of total PRL were higher, and serum levels of free PRL were lower, in pregnant women with anti-PRL autoantibodies than in pregnant women without macroprolactinemia.

Epidermal growth factor and gastrin in scleroderma/CREST syndrome.

BACKGROUND: The objective of this study was to determine levels of epidermal growth factor (EGF) and gastrin (GA) in saliva, serum, and urine in scleroderma (Scl) and CREST syndrome. METHODS: EGF and GA levels were measured by radioimmunoassay in saliva, serum and urine in 10 patients (51 years, median; range, 35-66 years); 9 females and 1 male with Scl, 3 females with CREST syndrome, and 18 age- and sex-matched controls, 17 females and 1 male free of any systemic inflammatory disease. RESULTS: In serum, the EGF was lower in Scl/CREST than controls (p = 0.02), while GA serum concentrations were higher in Scl/CREST (p = 0.02). In urine, EGF in Scl/CREST was slightly lower than controls (p = NS) and GA concentrations were higher than controls (p = 0.03). In saliva, the EGF levels in Scl/CREST were also slightly lower than controls (p = NS), while GA concentrations in both Scl/CREST and controls were not different (p = NS). CONCLUSIONS: Low concentrations of EGF in serum probably play a role in the pathogenesis of Scl/CREST. GA concentration can be increased as a consequence of the low levels of EGF because of the structural homology of this peptide with urogastrone, a GA inhibitor factor.

[Participation of hormones and regulating factors in implantation and development of the fetoplacental unit]. / Participación de hormonas y factores reguladores de la implantación y el desarrollo de la unidad fetoplacentaria.

Although the embryo has a genetic program of its own development in order that development and embryonic differentiation take place, as well as normal gestation, a series of coordinated interactions between embryo and the mother, should be established; which are mediated by chemical messengers, autocrine, paracrine and endocrine. In this study, hormonal participation and regulating factors of implantation, and the feto-placental unit development, are analyzed.

[Rosette-forming lymphocytes in the peripheral blood of normal children]. / Linfocitos formadores de rosetas en sangre periférica de niños normales.

The study included 180 healthy children distributted into age groups from newborns to 16 years of age. The subpopulations of early E and EAC (T and B) rosette forming lymphocytes were determined. It was found that the main difference is placed in percentual mean values of the newborn where the value of T lymphocytes is less than for the rest of the ages studied, remaining stable beginning at the age of one year. In newborns, the values of B lymphocytes are greater; later, they drop but remain stable also since the age of one.