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Serum protein electrophoresis in HIV seropositive and seronegative pregnant women
International Journal of Gynecology and Obstetrics 84 (2004) 254–258
Brief communication
Serum protein electrophoresis in HIV seropositive and seronegative pregnant women L.C. Kapsenberga,1, H.S. Cronje´ a,*, H. van Jaarsveldb a
Departments of Obstetrics and Gynecology, University of the Free State, Bloemfontein, South Africa b Department of Chemical Pathology, University of the Free State, Bloemfontein, South Africa Received 28 February 2003; received in revised form 8 July 2003; accepted 15 July 2003
Keywords: Electrophoresis; Immunoglobulin; HIV; Pregnancy
Both HIV infection and pregnancy have a suppressive effect on the immune system w1,2x. The subsequent question is what effect do these two conditions have on each other? In this study we investigated the changes in the immunoglobulin patterns of HIV seropositive and seronegative pregnant women. Protein electrophoresis was performed on the serum of every new patient admitted to the High Risk Obstetric Unit (HROU) of the Universitas Hospital, Bloemfontein, South Africa between 1 April and 30 November 2001. In addition, the HIV status, total CD4q cell count, and the immunoglobulin serum levels was determined for every patient. All patients who tested positive for HIV infection were included and the two patients who tested negative before and after each positive case were included as controls. Fifty-one HIV positive cases and 102 HIV negative controls were matched, a total of 153 *Corresponding author. Tel.: q27-51-4053444; fax: q2751-4442660. E-mail address: ´ [email protected] (H.S. Cronje). 1 Present address: Department of Obstetrics and Gynecology, University of Groningen, The Netherlands.
patients. Demographic, reproductive and clinical data are described in Table 1. The laboratory data according to HIV status are given in Table 2. Compared to the controls, the HIV seropositive women presented with the following significant differences: decreased CD4q cell count and serum albumin; increased total protein and g-globulin (P-0.01). The electrophoretograms of the HIV seropositive women revealed oligoclonal bands andyor an elevated protein concentration in the middle of the g-globulin fraction (noted only in HIV seropositive patients, P-0.01). The two groups were also compared using a CD4q cell count -0.4=109 yl in order to evaluate the effect of HIV infection in patients with low CD4q cell counts (Table 3). In addition to elevated g-globulin fractions, HIV seropositive women revealed increased serum IgG and IgM levels (P-0.01 and Ps0.03, respectively). Significantly more infections were diagnosed on admission in the HIV seropositive women than in the controls (35.3% vs. 19.6%, Ps0.03). Viral infections and tuberculosis were mainly responsible for this difference.
0020-7292/04/$30.00 䊚 2003 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijgo.2003.07.005
HIV seropositive (ns51)
HIV seronegative (ns102)
P-value
Median age (years)
27
27
0.51
Race: Black Colored White
50 (98.0%) 1 (2.0%) 0 (0%)
90 (88.2%) 8 (7.8%) 4 (3.9%)
0.07 0.27 0.30
1.0%; 16.5% y11.9%; 2.0% y7.7%; 1.8%
Obstetric indices: Gravidity (median) Primigravida Reproductive failurea
2 15 (29.4%) 14 (38.9%)
2 36 (35.3%) 26 (39.4%)
0.52 0.47 0.96
y3; 1 y20.8%; 10.0% y19.7%; 19.2%
GAb (weeks): GA at electrophoresis (median) GA at delivery (median)
30 32
31 32
0.29 0.25
y3; 1 y1; 0
Main reasons for admittance: Hypertensive disorder Cardiac disease Antepartum hemorrhage Diabetes mellitus Preterm labor (imminent)
26 3 4 4 5
0.42 0.25 0.73 0.48 1.00
y23.3%; y14.2%; y6.2%; y5.1%; y9.4%;
(51.0%) (5.9%) (7.8%) (7.8%) (9.8%)
59 12 6 5 10
(57.8%) (11.8%) (5.9%) (4.9%) (9.8%)
95% CI for differences y3; 2
9.8% 4.2% 11.6% 12.4% 10.9%
The results are presented as median and numbers (percentages). a Reproductive failure was defined as the occurrence of a miscarriage, fetal loss, ectopic pregnancy or neonatal death in the obstetric history (all primigravida were excluded). b GA, gestational age.
L.C. Kapsenberg et al. / International Journal of Gynecology and Obstetrics 84 (2004) 254–258
Table 1 Demographic, reproductive and clinical data according to HIV status
255
256
HIV seropositive (ns51)
HIV seronegative (ns102)
P-value
CD4q cell count (=109 yl) Total serum protein (gyl) Serum albumin (gyl)
0.34 (0.2, 0.5) 62.0 (56.0, 77.0) 21.0 (18.0, 27.0)
0.69 (0.5, 1.0) 57.0 (52.0, 63.0) 24.5 (21.0, 28.0)
-0.01 -0.01 -0.01
Serum electrophoresis: Albumin fraction (gyl) Albumin of total serum protein (%) a 1-globulin fraction (gyl) a 2-globulin fraction (gyl) b-globulin fraction (gyl) g-globulin fraction (gyl) g-globulin of total serum protein (%) Hypergammaglobulinemiaa Hypogammaglobulinemiab
28.9 (24.1, 34.9) 48.6 (41.1, 56.5) 2.89 (2.2, 3.4) 6.02 (4.8, 8.0) 8.16 (7.4, 9.6) 13.55 (10.3, 19.8) 22.3 (17.3, 30.4) 25 (49.0%) 2 (3.9%)
33.0 (28.0, 38.0) 59.3 (54.6, 62.5) 2.74 (2.2, 3.4) 6.16 (5.1, 7.1) 8.41 (7.5, 9.4) 5.55 (4.1, 8.3) 9.8 (7.4, 13.9) 4 (3.9%) 45 (44.1%)
0.01 -0.01 0.83 0.74 0.86 -0.01 -0.01 -0.01 -0.01
y5.7; y0.7 y13.0; y6.6 y0.3; 0.4 y0.6; 0.8 y0.6; 0.5 6.1; 9.5 9.5; 14.3 30.2%; 58.4% y49.7%; y27.5%
Serum electrophoresis description: Normal Oligoclonal bands Elevated PCc in g-globulin fraction
9 (17.1%) 15 (30.0%) 26 (52.0%)
52 (51.5%) 0 (0%) 2 (2.0%)
-0.01 -0.01 -0.01
y48.2%; y20.2% 17.2%; 42.5% 35.1%; 63.0%
Immunoglobulin serum levels: IgG (gyl) IgA (gyl) IgM (gyl) IgE (IUyml)
16.75 (14.3, 22.5) 1.97 (1.2, 3.1) 1.78 (1.2, 2.7) 49(20, 186)
9.91 (8.1, 11.8) 1.92 (1.6, 2.6) 1.17 (0.8, 1.8) 71 (19, 157)
-0.01 0.82 -0.01 0.85
5.9; 8.9 y0.4; 0.3 0.3; 0.8 y23; 23
Results are presented as median (quartiles) and numbers (percentages). a Diagnosis of hypergammaglobulinemia was made when the g-globulin concentration was )13.7 gyl. b Diagnosis of hypogammaglobulinemia was made when the g-globulin concentration was -5.3 gyl. c PC, protein concentration.
95% CI for differences y0.5; y0.3 2; 9 y5; y1
L.C. Kapsenberg et al. / International Journal of Gynecology and Obstetrics 84 (2004) 254–258
Table 2 Laboratory data according to HIV status
HIV seropositive (ns31)
HIV seronegative (ns16)
P-value
Immunoglobulines: IgG (gyl) IgM (gyl)
15.70 (14.1, 21.2) 1.78 (1.2, 2.9)
10.55 (9.1, 11.6) 1.24 (0.9, 1.6)
-0.01 0.03
3.7; 8.3 0.1; 1.2
Serum electrophoresis: g-globulin fraction (gyl) g-globulin of total serum protein (%) Albumin fraction (gyl) Albumin of total serum protein (%) Total serum protein (gyl)
13.18 (10.9, 19.5) 21.2 (18.3, 31.0) 28.81 (22.45, 34.34) 47.7 (40.4, 54.6) 60.0 (54.0, 67.0)
5.47 (4.5, 7.1) 8.8 (7.6, 12.2) 34.02 (30.48, 38.47) 59.4 (54.4, 61.8) 61.0 (56.5, 64.0)
-0.01 -0.01 0.01 -0.01 0.76
5.3; 9.6 8.1; 17.4 y10.5; y1.8 y16.4; y4.9 y4; 6
Laboratory data
Results are presented as median (quartiles).
95% CI for differences
L.C. Kapsenberg et al. / International Journal of Gynecology and Obstetrics 84 (2004) 254–258
Table 3 Laboratory data according to HIV status in patients with CD4q cell counts -0.4=109yl
257
258
L.C. Kapsenberg et al. / International Journal of Gynecology and Obstetrics 84 (2004) 254–258
Although some of the abnormal serum protein pattern may have been caused by infections, the numbers of infected patients were too small to significantly influence the electrophoretograms. HIV infection was mainly responsible for the observed abnormalities. Most of the HIV seropositive women (79%) revealed a raised g-globulin fraction (hypergammaglobulinemia and oligoclonal bands) compared to only 3.9% of the controls. Most characteristic was the presence of oligoclonal bands against a polyclonal background in addition to the raised g-globulin for HIV seropositive women (Fig. 1). Oligoclonal bands are not diagnostic of AIDS, but seem to correspond with disease progression. With advanced disease, however, they may disappear again w3x. References w1x Watanabe M, Iwatani Y, Hidaka Y, Mitsuda N, Amino N. Changes in soluble CD4 and CD8 proteins in healthy pregnant and postpartum women. Am J Reprod Immunol 1996;36:220 –227. w2x Fauci AS. The human immunodeficiency virus: infectivity and mechanisms of pathogenesis. Science 1988;239: 617 –622. w3x Papadopoulos NM, Costello R, Ceroni M, Moutsopoulos HM. Identification of HIV-specific oligoclonal immunoglobulins in serum of carriers of HIV antibody. Clin Chem 1988;34:973 –975.
Fig. 1. Serum electrophoresis of the HIV seronegative and seropositive women.
Brief communication
Serum protein electrophoresis in HIV seropositive and seronegative pregnant women L.C. Kapsenberga,1, H.S. Cronje´ a,*, H. van Jaarsveldb a
Departments of Obstetrics and Gynecology, University of the Free State, Bloemfontein, South Africa b Department of Chemical Pathology, University of the Free State, Bloemfontein, South Africa Received 28 February 2003; received in revised form 8 July 2003; accepted 15 July 2003
Keywords: Electrophoresis; Immunoglobulin; HIV; Pregnancy
Both HIV infection and pregnancy have a suppressive effect on the immune system w1,2x. The subsequent question is what effect do these two conditions have on each other? In this study we investigated the changes in the immunoglobulin patterns of HIV seropositive and seronegative pregnant women. Protein electrophoresis was performed on the serum of every new patient admitted to the High Risk Obstetric Unit (HROU) of the Universitas Hospital, Bloemfontein, South Africa between 1 April and 30 November 2001. In addition, the HIV status, total CD4q cell count, and the immunoglobulin serum levels was determined for every patient. All patients who tested positive for HIV infection were included and the two patients who tested negative before and after each positive case were included as controls. Fifty-one HIV positive cases and 102 HIV negative controls were matched, a total of 153 *Corresponding author. Tel.: q27-51-4053444; fax: q2751-4442660. E-mail address: ´ [email protected] (H.S. Cronje). 1 Present address: Department of Obstetrics and Gynecology, University of Groningen, The Netherlands.
patients. Demographic, reproductive and clinical data are described in Table 1. The laboratory data according to HIV status are given in Table 2. Compared to the controls, the HIV seropositive women presented with the following significant differences: decreased CD4q cell count and serum albumin; increased total protein and g-globulin (P-0.01). The electrophoretograms of the HIV seropositive women revealed oligoclonal bands andyor an elevated protein concentration in the middle of the g-globulin fraction (noted only in HIV seropositive patients, P-0.01). The two groups were also compared using a CD4q cell count -0.4=109 yl in order to evaluate the effect of HIV infection in patients with low CD4q cell counts (Table 3). In addition to elevated g-globulin fractions, HIV seropositive women revealed increased serum IgG and IgM levels (P-0.01 and Ps0.03, respectively). Significantly more infections were diagnosed on admission in the HIV seropositive women than in the controls (35.3% vs. 19.6%, Ps0.03). Viral infections and tuberculosis were mainly responsible for this difference.
0020-7292/04/$30.00 䊚 2003 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijgo.2003.07.005
HIV seropositive (ns51)
HIV seronegative (ns102)
P-value
Median age (years)
27
27
0.51
Race: Black Colored White
50 (98.0%) 1 (2.0%) 0 (0%)
90 (88.2%) 8 (7.8%) 4 (3.9%)
0.07 0.27 0.30
1.0%; 16.5% y11.9%; 2.0% y7.7%; 1.8%
Obstetric indices: Gravidity (median) Primigravida Reproductive failurea
2 15 (29.4%) 14 (38.9%)
2 36 (35.3%) 26 (39.4%)
0.52 0.47 0.96
y3; 1 y20.8%; 10.0% y19.7%; 19.2%
GAb (weeks): GA at electrophoresis (median) GA at delivery (median)
30 32
31 32
0.29 0.25
y3; 1 y1; 0
Main reasons for admittance: Hypertensive disorder Cardiac disease Antepartum hemorrhage Diabetes mellitus Preterm labor (imminent)
26 3 4 4 5
0.42 0.25 0.73 0.48 1.00
y23.3%; y14.2%; y6.2%; y5.1%; y9.4%;
(51.0%) (5.9%) (7.8%) (7.8%) (9.8%)
59 12 6 5 10
(57.8%) (11.8%) (5.9%) (4.9%) (9.8%)
95% CI for differences y3; 2
9.8% 4.2% 11.6% 12.4% 10.9%
The results are presented as median and numbers (percentages). a Reproductive failure was defined as the occurrence of a miscarriage, fetal loss, ectopic pregnancy or neonatal death in the obstetric history (all primigravida were excluded). b GA, gestational age.
L.C. Kapsenberg et al. / International Journal of Gynecology and Obstetrics 84 (2004) 254–258
Table 1 Demographic, reproductive and clinical data according to HIV status
255
256
HIV seropositive (ns51)
HIV seronegative (ns102)
P-value
CD4q cell count (=109 yl) Total serum protein (gyl) Serum albumin (gyl)
0.34 (0.2, 0.5) 62.0 (56.0, 77.0) 21.0 (18.0, 27.0)
0.69 (0.5, 1.0) 57.0 (52.0, 63.0) 24.5 (21.0, 28.0)
-0.01 -0.01 -0.01
Serum electrophoresis: Albumin fraction (gyl) Albumin of total serum protein (%) a 1-globulin fraction (gyl) a 2-globulin fraction (gyl) b-globulin fraction (gyl) g-globulin fraction (gyl) g-globulin of total serum protein (%) Hypergammaglobulinemiaa Hypogammaglobulinemiab
28.9 (24.1, 34.9) 48.6 (41.1, 56.5) 2.89 (2.2, 3.4) 6.02 (4.8, 8.0) 8.16 (7.4, 9.6) 13.55 (10.3, 19.8) 22.3 (17.3, 30.4) 25 (49.0%) 2 (3.9%)
33.0 (28.0, 38.0) 59.3 (54.6, 62.5) 2.74 (2.2, 3.4) 6.16 (5.1, 7.1) 8.41 (7.5, 9.4) 5.55 (4.1, 8.3) 9.8 (7.4, 13.9) 4 (3.9%) 45 (44.1%)
0.01 -0.01 0.83 0.74 0.86 -0.01 -0.01 -0.01 -0.01
y5.7; y0.7 y13.0; y6.6 y0.3; 0.4 y0.6; 0.8 y0.6; 0.5 6.1; 9.5 9.5; 14.3 30.2%; 58.4% y49.7%; y27.5%
Serum electrophoresis description: Normal Oligoclonal bands Elevated PCc in g-globulin fraction
9 (17.1%) 15 (30.0%) 26 (52.0%)
52 (51.5%) 0 (0%) 2 (2.0%)
-0.01 -0.01 -0.01
y48.2%; y20.2% 17.2%; 42.5% 35.1%; 63.0%
Immunoglobulin serum levels: IgG (gyl) IgA (gyl) IgM (gyl) IgE (IUyml)
16.75 (14.3, 22.5) 1.97 (1.2, 3.1) 1.78 (1.2, 2.7) 49(20, 186)
9.91 (8.1, 11.8) 1.92 (1.6, 2.6) 1.17 (0.8, 1.8) 71 (19, 157)
-0.01 0.82 -0.01 0.85
5.9; 8.9 y0.4; 0.3 0.3; 0.8 y23; 23
Results are presented as median (quartiles) and numbers (percentages). a Diagnosis of hypergammaglobulinemia was made when the g-globulin concentration was )13.7 gyl. b Diagnosis of hypogammaglobulinemia was made when the g-globulin concentration was -5.3 gyl. c PC, protein concentration.
95% CI for differences y0.5; y0.3 2; 9 y5; y1
L.C. Kapsenberg et al. / International Journal of Gynecology and Obstetrics 84 (2004) 254–258
Table 2 Laboratory data according to HIV status
HIV seropositive (ns31)
HIV seronegative (ns16)
P-value
Immunoglobulines: IgG (gyl) IgM (gyl)
15.70 (14.1, 21.2) 1.78 (1.2, 2.9)
10.55 (9.1, 11.6) 1.24 (0.9, 1.6)
-0.01 0.03
3.7; 8.3 0.1; 1.2
Serum electrophoresis: g-globulin fraction (gyl) g-globulin of total serum protein (%) Albumin fraction (gyl) Albumin of total serum protein (%) Total serum protein (gyl)
13.18 (10.9, 19.5) 21.2 (18.3, 31.0) 28.81 (22.45, 34.34) 47.7 (40.4, 54.6) 60.0 (54.0, 67.0)
5.47 (4.5, 7.1) 8.8 (7.6, 12.2) 34.02 (30.48, 38.47) 59.4 (54.4, 61.8) 61.0 (56.5, 64.0)
-0.01 -0.01 0.01 -0.01 0.76
5.3; 9.6 8.1; 17.4 y10.5; y1.8 y16.4; y4.9 y4; 6
Laboratory data
Results are presented as median (quartiles).
95% CI for differences
L.C. Kapsenberg et al. / International Journal of Gynecology and Obstetrics 84 (2004) 254–258
Table 3 Laboratory data according to HIV status in patients with CD4q cell counts -0.4=109yl
257
258
L.C. Kapsenberg et al. / International Journal of Gynecology and Obstetrics 84 (2004) 254–258
Although some of the abnormal serum protein pattern may have been caused by infections, the numbers of infected patients were too small to significantly influence the electrophoretograms. HIV infection was mainly responsible for the observed abnormalities. Most of the HIV seropositive women (79%) revealed a raised g-globulin fraction (hypergammaglobulinemia and oligoclonal bands) compared to only 3.9% of the controls. Most characteristic was the presence of oligoclonal bands against a polyclonal background in addition to the raised g-globulin for HIV seropositive women (Fig. 1). Oligoclonal bands are not diagnostic of AIDS, but seem to correspond with disease progression. With advanced disease, however, they may disappear again w3x. References w1x Watanabe M, Iwatani Y, Hidaka Y, Mitsuda N, Amino N. Changes in soluble CD4 and CD8 proteins in healthy pregnant and postpartum women. Am J Reprod Immunol 1996;36:220 –227. w2x Fauci AS. The human immunodeficiency virus: infectivity and mechanisms of pathogenesis. Science 1988;239: 617 –622. w3x Papadopoulos NM, Costello R, Ceroni M, Moutsopoulos HM. Identification of HIV-specific oligoclonal immunoglobulins in serum of carriers of HIV antibody. Clin Chem 1988;34:973 –975.
Fig. 1. Serum electrophoresis of the HIV seronegative and seropositive women.