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

Abstract

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 immunoradio-metric 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 macro-prolactinemia was ≥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 ≥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.

Keywords

hyperprolactinemia macroprolactinemia anti-prolactin autoantibody polyethylene glycol diagnostic test

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References

Garnier PE , Aubert ML , Kaplan SL , Grumbach MM . Heterogeneity of pituitary and plasma prolactin in man: decreased affinity of ‘big‘ prolactin in a radioreceptor assay and evidence for its secretion . J Clin Endocrinol Metab 1978; 47: 1273–1281 .

Farkouh NH , Packer MG , Frantz AG . Large molecular size prolactin with reduced receptor activity in human serum: high proportion in basal state and reduction after thyrotropin-releasing hormone . J Clin Endocrinol Metab 1979; 48: 1026–1032 .

Soong YK , Ferguson KM , McGarrick G , Jeffcoaate SL . Size heterogeneity of immunoreactive prolactin in hyperprolactinemic serum . Clin Endocrinol (Oxf) 1982; 16: 259–265 .

Larrea F , Escorza A , Granados J et al. Familial occurrence of big-big prolactin as the predominant immunoreactive human prolactin species in blood . Fertil Steril 1987; 47: 956–963 .

Tanaka T , Yano H . Umezawa S et al. Heterogeneity of big-big hPRL in hyperprolactinemia . Horm Metab Res 1989; 21: 84–88 .

Sinha YN . Structural variants of prolactin: occurrence and physiological significance . Endocr Rev 1995; 16: 354–369 .

Fraser IS , Lun ZG , Zhou JP et al. Detailed assessment of big-big prolactin in women with hyperprolactinemia an normal ovarian function . J Clin Endocrinol Metab 1989; 69: 585–592 .

Hattori N , Ikekubo K , Ishihara T , Moridera K , Hino M , Kurahachi K . A normal ovulatory woman with hyperprolactinemia: presence of antiprolactin autoantibody and the regulation of prolactin secretion . Acta Endocrinol 1992; 126: 497–500 .

Hattori N , Ishihara T , Ikekubo K , Moridera K , Hino M , Kurahachi H . Autoantibody to human prolactin in patients with idiopathic hyperprolactinemia . J Clin Endocrinol Metab 1992; 75: 1226–1229 .

10.

McMurray R , Keisler D , Kanuekel K , Izui S , Walker SE . Prolactin influences autoimmune disease activity in the female B/W mouse . J Immunol 1991; 147: 780–787 .

11.

Lavalle C , Loyo E , Paniagua R et al. Correlation study between prolactin and androgens in male patients with systemic lupus erythematosus . J Rheumatol 1987; 14: 268–272 .

12.

Folomeev M , Prokaeva T , Nassonova V . Proloactin levels in men with SLE and RA . J Rheumatol 1990; 17: 1569–1570 .

13.

Jara LJ , Gomez-Sanchez C , Silveira LH , Martinez-Osuna P , Vassey FB , Espinoza LR . Hyperprolactinemia in systemic lupus erythematosus: association with disease activity . Am J Med Sci 1992; 303: 222–226 .

14.

Buskila D , Lorber M , Neumann L , Flusser D , Shoenfeld Y . No correlation between prolactin levels and clinical activity in patients with systemic lupus erythematosus . J Rheumatol 1996; 23: 629–632 .

15.

Pauzner R , Urowitz MB , Gladman DD , Cough J . Prolactin in systemic lupus erythematosus . J Rheumatol 1994; 21: 2064–2067 .

16.

Neidhart M . Elevated serum prolactin or elevated prolactin/cortisol ratio are associated with autoimmune processes in systemic lupus erythematosus and other connective tissue diseases . J Rheumatol 1996; 23: 476–481 .

17.

Ostendorf B , Fischer R , Santen R , Schmitz-Linneweber B , Specker Ch , Schneider M . Hyperprolactinemia in systemic lupus erythematosus? Scand J Rheumatol 1996; 25: 97–102 .

18.

Blanco-Favela F , Quintal-Alvarez G , Leaños-Miranda A . Association between prolactin and disease activity in SLE . Influence of statistical power. J Rheumatol 1999; 26: 55–59 .

19.

Leaños A , Pascoe D , Fraga A , Blanco F . Anti-prolactin autoantibodies in systemic lupus erythematosus patients with associated hyperprolactinemia . Lupus 1998; 7: 398–403 .

20.

Hattori N , Ikekubo K , Ishihara T , Moridera K , Hino M , Kurahachi H . Effects of anti-prolactin autoantibodies on serum prolactin measurements . Eur J Endocrinol 1994; 130: 434–437 .

21.

Schultze HE , Heremans JF . In: Molecular Biology of Human Proteins. Elsevier: Amsterdam , 1996, p 256–256.

22.

Polson A . The fractionation of protein mixture by linear polymers of high molecular weight . Biochem Biophys Acta 1965; 94: 581–581 .

23.

Zeppezauer M , Bishammer S . Protein precipitation by uncharged water soluble polymers . Biochem Biophys Acta 1965; 94: 581–581 .

24.

Iverius PH , Laurent TC . Precipitation of some plasma proteins by addition of dextran or polyethylene glycol . Biochem Biophys Acta 1967; 331: 371–371 .

25.

Tan EM , Cohen AS , Fries JF et al. The 1982 revised criteria for the classification of systemic lupus erythematosus . Arthritis Rheum 1982; 25: 1271–1277 .

26.

Vance ML , Thorner MO . Prolactin: hyperprolactinemic syndromes and management. In: De Groot LJ (eds). Endocrinology, 2nd edn. WB Saunders: Philadelphia, PA , 1989, p 408–408.

27.

Leaños-Miranda A , Pascoe-Lira D , Blanco-Favela F . Prolactin and systemic lupus erythematosus . (Letter.) Br J Rheumatol 1998; 37: 1029–1030 .

28.

Hanley JA , McNeil BJ . The meaning and use of the area under a receiver operating characteristic (ROC) curve . Radiology 1982; 143: 29–36 .

29.

Fahie-Wilson MN , Soule SG . Macroprolactinaemia in a district general hospital an evaluation of a screening test based on precipitation with polyethylene glycol . Ann Clin Biochem 1997; 34: 252–258 .

30.

Olukoga AO , Kane JW . Macroprolactinaemia: validation and application of the polyethylene glycol precipitation test and clinical characterization of the condition . Clin Endocrinol (Oxf) 1999; 51: 119–126 .