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596 Am J Clin Pathol 2007;128:596-603596 DOI: 10.1309/QWTQFGA9FXN02YME

© American Society for Clinical Pathology

Immunopathology / MONOCLONAL BANDING IN HIV PATIENTS

Protein Electrophoresis and Immunoglobulin Analysisin HIV-Infected Patients

Panagiotis A. Konstantinopoulos, MD, PhD,1 Bruce J. Dezube, MD,1 Liron Pantanowitz, MD,2

Gary L. Horowitz, MD,3 and Bruce A. Beckwith, MD3

Key Words: HIV; Protein electrophoresis; Monoclonal banding; Immunoglobulins

DOI: 10.1309/QWTQFGA9FXN02YME

A b s t r a c t

We studied the prevalence and nature of

immunoglobulin abnormalities in HIV-1–infected

patients in the era of highly active antiretroviral

therapy. Protein electrophoreses (PEP) were performed

on and quantitative immunoglobulin levels obtained in

samples from 320 consecutive HIV-1–infected patients.

Samples with possible PEP abnormalities underwent

immunofixation. The PEP pattern was normal in 83.8%

of samples, 8.1% had subtle oligoclonal banding, and 4.4% had a low-concentration (<5% of total protein)

monoclonal band. Hypogammaglobulinemia and

polyclonal hypergammaglobulinemia accounted for

1.9% each. In multivariate analysis, younger age (odds

ratio [OR], 1.06 with each decreasing year of life; 95%

confidence interval [CI], 1.02-1.11; P = .016), female

sex (OR, 2.4; 95% CI, 1.13-5.11; P = .02), viral load

(OR, 1.50 with each increasing logarithmic viral load

of 1.0; 95% CI, 1.14-1.98; P = .004), and CD4 cell

count (≥350 vs <350/µL [0.35 × 109 /L]) (OR, 2.71;

95% CI, 1.09-6.75; P = .032) were associated withmonoclonal or oligoclonal banding. These results

suggest that younger HIV-1–infected patients with a

more robust immune system (higher CD4 cell count),

which is stimulated by uncontrolled viremia, are most

likely to have an augmented B-cell response to HIV

infection. One manifestation of this B-cell response is

low-concentration monoclonal banding in 4.4% of the

patients studied.

Early in the investigation of AIDS, it was recognized that

many patients showed abnormal immunoglobulin patterns by

protein electrophoresis (PEP).1 These abnormalities included

polyclonal hypergammaglobulinemia, which may be striking,

hypogammaglobulinemia, and oligoclonal banding and mono-

clonal immunoglobulin bands.2 Over the years, there have

also been case reports of plasma cell dyscrasias occurring in

HIV+ patients.3-5 Although still uncommon, the incidence of

plasma cell neoplasia associated with HIV infection may be

increasing.6

The widespread adoption of highly active antiretroviral

therapy (HAART) since 1997 has dramatically altered the

treatment of and prognosis for HIV+ patients.7,8 As early as

1999, it was reported that HAART reduced monoclonal pro-

tein concentrations in HIV patients.8,9 Given these dramatic

changes in treatment, disease course, and life expectancy, cou-

pled with the increased resolution and sensitivity of available

protein electrophoresis systems in clinical laboratories, we

sought to study the current electrophoresis patterns in a cohort

of HIV+ patients. The aim of the present study was to exam-

ine the prevalence and nature of PEP abnormalities present incontemporary patients with HIV and to identify factors that

may be associated with these abnormalities.

Materials and Methods

Sample Selection

The study was designed to look at samples from a brief

cross-section of all patients with HIV at Beth Israel Deaconess

Medical Center, Boston, MA (our institution). During the

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Immunopathology / ORIGINAL ARTICLE

study period (October and November 2003), we tested a plas-

ma sample (to be discarded) from each consecutive unique

patient with HIV for whom a specimen was submitted to our

laboratory for quantitative HIV viral load determination and a

concurrent CD4 cell count was performed. In our institution,

PEP is ordered for approximately 9% of known HIV+

patients, whereas 0.4% of all PEPs done in our institution are

performed on HIV-infected patients. The Committee on

Clinical Investigations at our institution approved the protocol

for this study. Patient demographics (age and sex) were

recorded. We were unable to obtain adequate information

regarding antiretroviral therapy. HIV viral load results (Cobas

Amplicor PCR, Roche Diagnostics, Indianapolis, IN) and

CD4+ T-cell counts (4-color flow cytometric analysis using a

FACSCalibur instrument, Becton Dickinson, San Jose, CA,

using their Multiset software) were obtained from the clinical

records of all patients.

Immunoglobulin Measurements

Measurement of total IgG, IgA, and IgM levels (Tina-

quant, Roche Diagnostics) were performed on all samples.

Electrophoresis, Immunofixation, and Densitometry

Electrophoresis (Hydrasys, Sebia, Norcross, GA) was

performed on all samples. The electrophoretic gels were

reviewed independently by 3 pathologists (L.P., G.L.H., and

B.A.B.). Immunofixation (Hydrasys) was performed on sam-

ples when abnormalities were detected. The electrophoretic

patterns were categorized as normal, hypogammaglobuline-

mia, polyclonal hypergammaglobulinemia, oligoclonal band-ing (≥2 discrete bands of immunoglobulin confirmed by

immunofixation), or monoclonal band (1 discrete band of

immunoglobulin confirmed by immunofixation). For samples

with a single monoclonal band, the intensity of the band was

measured by densitometry (Phoresis software, Sebia), and the

total protein value was obtained (Hitachi 917, Roche

Diagnostics). The final determination of the pattern was made

by comparing the interpretations of all pathologists and, when

different, reviewing the gels together to reach a consensus

interpretation.

Statistical Analysis

Differences in immunoglobulin levels, age, CD4 cell

counts, and viral loads between males and females and

between patients with or without monoclonal and/or oligo-

clonal banding were investigated by using the independent-

samples t test. For analyses using viral load, the logarithm of

the viral load was always used. Our method has a limit of

detection of 50 copies per milliliter. For the purposes of statis-

tical analysis, samples with undetected viral loads were treat-

ed as 50 copies per milliliter. Associations between sex and

age (<40 vs ≥40 years), CD4 cell count (high or low using a

cutoff of 350 cells/µL [0.35 × 109 /L]), and detectable viral

load were evaluated by using the χ2 test. Associations between

banding (monoclonal or oligoclonal) and sex, CD4 cell count

(high or low using the aforementioned cutoff), viral load

(detected or undetected), and age (<40 vs ≥40 years) were also

evaluated by using the χ2 test. Logistic regression was per-

formed using banding as the dependent variable and age, sex,

CD4 cell count, and viral load each as sole covariates.

After significant variables were identified in the univari-

ate analysis, forward stepwise logistic regression was per-

formed using combinations of these variables until the best

multivariate logistic regression model was determined.

Statistical calculations were performed by using SPSS soft-

ware, version 9.0 (SPSS, Chicago, IL).

Results

Patient Characteristics

The patient population included 253 males and 67

females. Patient characteristics are given in ❚Table 1❚. Ages

ranged from 7 to 67 years (median, 42 years). The mean age

of females (41.1 years) was slightly younger than that of

❚Table 1❚HIV+ Patient Baseline Characteristics and Immunoglobulin Concentrations in 320 Cases

Characteristic Female (n = 67) Male (n = 253) P

Mean age (y) 41.1 43.5 .023*

No. (%) age <40 y 29 (43) 71 (28.1) .026†

Mean CD4 cell count/µL (× 109 /L) 563.9 (0.56) 556.4 (0.56) .867*

Mean log HIV viral load (copies/mL) 2.8318 2.7634 .704*

No. (%) with undetected HIV viral load (copies/mL) 29 (43) 116 (45.8) .881†

No. (%) with CD4 cell count <350/µL (× 109 /L) 19 (28) 76 (30.0) .783†

Mean IgG, mg/dL (g/L) 2,022.3 (20.2) 1,534.9 (15.3) <.001*

Mean IgA, mg/dL (mg/L) 258.7 (2,587) 305.23 (3,052) .072*

Mean IgM, mg/dL (mg/L) 134.6 (1,346) 119.2 (1,192) .231*

* Independent samples t test.† χ2 test.

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Konstantinopoulos / MONOCLONAL BANDING IN HIV PATIENTS

males, and this difference was statistically significant.

Correspondingly, there was a higher percentage of females

younger than 40 years compared with males.

There was no statistically significant difference in the

viral load and CD4 cell counts between male and female

patients (Table 1). Furthermore, there was no statistically sig-

nificant difference between the percentages of male and

female patients who had an undetected viral load. Similarly,

there was no statistically significant difference between the

percentages of male and female patients who had a low CD4

count less than the cutoff.

Immunoglobulin Concentrations

The median concentrations of immunoglobulins among

all patients were as follows: IgG, 1,518 mg/dL (15.18 g/L;

range, 410-3,791 mg/dL [4.1-37.91 g/L]); IgA, 254 mg/dL

(2,540 mg/L; range, 8-1,332 mg/dL [80-13,320 mg/L]); and

IgM, 94 mg/dL (940 mg/L; range, 40-572 mg/dL [400-5,720

mg/L]). There were differences when the immunoglobulin

concentrations were analyzed by sex: Females had higher

average levels of IgG, but differences in IgM and IgA did not

reach statistical significance.

By using the reference ranges recommended by the assay

manufacturer (IgG, 7-16 g/L; IgA, 700-4,000 mg/L; and IgM,

400-2,300 mg/L), samples were also classified as having

decreased, normal, or increased levels of specific

immunoglobulins. Overall, 139 had an elevated IgG concen-

tration, 72 had an increased IgA level, and 35 had an increased

IgM level. In 11 samples, levels of all 3 immunoglobulins

were increased, and in only 1 sample, levels of all 3immunoglobulins were decreased. Two statistically significant

differences were noted in immunoglobulin levels. Among

females, 51 (76%) had elevated levels of IgG, whereas for

males, the rate was lower, 89 (35.2%; P < .001; χ2). However,

63 males (24.9%) had increased IgA levels compared with

only 9 (13%) of females (P < .05; χ2).

Electrophoretic Patterns

The consensus interpretations of the protein elec-

trophoretic patterns are shown in ❚Table 2❚. Of the 14 mono-

clonal bands, 13 were of the IgG κ type and 1 was IgG λ. Allbands represented less than 5% (average, 2.1%) of the protein

present by densitometric measurement. Multiplication of the

densitometric measurement by the total protein concentration

allowed an estimate of the absolute concentration to be calcu-

lated in 12 cases (1 case did not have a total protein measure-

ment, and in 1 case, the monoclonal band overlaid a normal β

band). The estimated concentration of monoclonal protein

ranged from 0.3 to 4.65 g/L, with an average of 1.85 g/L. One

sample with a monoclonal band showed concomitant poly-

clonal hypergammaglobulinemia, and only 1 case had visual-

ly apparent hypogammaglobulinemia ❚Image 1❚. Among the

26 samples showing oligoclonal banding, 24 had only IgG

bands. Of these samples, 13 had κ and λ bands present, and 11

had only bands with a single light chain type identified. Two

oligoclonal samples had an IgA or IgM band in addition to an

IgG band.

Of 14 cases with monoclonal banding, data on stage and

treatment status were available for 12. Of the 12 patients rep-

resented, 11 received HAART at some point during their

infection. Eight were receiving HAART when the sample was

obtained, and 3 had received HAART in the past but were not

receiving it when the sample was obtained. Of the 12 patients,

2 had AIDS when the sample was obtained, and 10 had

asymptomatic HIV infection. The mean duration of HIV

infection in patients with monoclonal banding was 8.0 years

(the duration was known for 11 of 12 patients). These results

are given in ❚Table 3❚.

Factors Associated With Banding

To look for associations with electrophoretic patterns, thesamples were grouped into 2 categories by PEP interpretation:

(1) oligoclonal or monoclonal bands present (banding) or (2)

no bands seen (no banding). The distribution of different clin-

icopathologic characteristics among patients whose samples

demonstrated banding on PEP and those whose did not are

given in ❚Table 4❚ and in ❚Figure 1❚. In univariate analysis, age,

sex, and viral load were statistically significantly associated

with banding. Specifically, patients with banding were

younger (mean, 38.9 vs 43.6 years; P < .001) and had higher

average viral loads (logarithmic viral load, 3.34 vs 2.69; P =

.004) than patients without banding. Furthermore, femaleswere more likely than males to have any form of banding seen

on PEP. There was no statistically significant difference in the

CD4 cell count among patients with or without banding.

We further studied the associations between age, viral

load, and CD4 cell count with banding. Specifically, patients

younger than 40 years were more likely to show banding on

PEP than patients 40 years or older and this association

approached statistical significance (Table 4). Patients with a

detected viral load were more likely to show banding on PEP

than patients with an undetected viral load (Table 4). Finally,

there was a trend observed in which patients with CD4 cell

❚Table 2❚Electrophoretic Interpretation of 320 Plasma Samples From320 HIV+ Patients

Protein Electrophoresis Pattern No. of Patients (%)

Normal 268 (83.8)Oligoclonal banding 26 (8.1)Monoclonal band 14 (4.4)

Hypogammaglobulinemic 6 (1.9)Polyclonal hypergammaglobulinemic 6 (1.9)

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counts of 350/µL (0.35 × 109 /L) or more were more likely to

show banding on PEP than patients with CD4 cell counts of

less than 350/µL (0.35 × 109 /L), but this difference did notreach statistical significance (Table 4).

Logistic regression with banding as a dependent variable

and with age, logarithmic viral load, CD4 cell count, and sex

each as sole covariates demonstrated identical associations to

those with the χ2 test or t test. It is important to note that we

looked for possible interactions between sex, age, CD4 cell

count, and viral load by including interaction terms (eg, sex *

viral load, sex * CD4 cell count, age * sex) in the logisticregression, and there were no statistically significant interac-

tions identified.

After all significant variables (age, sex, and viral load)

were identified and interactions were excluded, forward step-

wise logistic regression was performed using combinations of

PEP IgG IgA IgM κ λ PEP IgG IgA IgM κ λ

A B

❚Image 1❚ Immunofixation electrophoresis gels from 2 HIV+ patients. From left to right, the tracks represent all proteins (labeled

PEP [protein electrophoresis pattern]), IgG, IgA, IgM, and κ and λ light chains. A, Oligoclonal banding is present in the γ region

with at least 3-4 bands of IgG κ and IgG λ immunoglobulins. The total IgG, IgA, and IgM levels were 3,694 mg/dL (36.9 g/L), 190

mg/dL (1,900 mg/L), and 199 mg/dL (1,990 mg/L), respectively. B, A single monoclonal band of IgG κ is seen in the γ region,

marked by the arrows. The total immunoglobulin levels were decreased (IgG, 410 mg/dL [4.1 g/L]; IgA, <8 mg/dL [80 mg/L]; and

IgM, <4 mg/dL [40 mg/L]). This was the only case that showed decreased levels of all 3 immunoglobulins and was also the only

case with a single monoclonal band occurring concomitantly with decreased immunoglobulin levels.

❚Table 3❚Characteristics of 14 Patients With Monoclonal Banding

Case No. Stage Therapy Status Duration of HIV Infection (y)

1 Asymptomatic HAART 42 Asymptomatic HAART 63 Unknown Unknown Unknown4 AIDS HAART 155 Asymptomatic HAART 76 Asymptomatic None when sample obtained; received HAART in the past 157 Asymptomatic None when sample obtained; received HAART in the past Unknown8 Asymptomatic None when sample obtained; received HAART in the past 69 Asymptomatic HAART 210 Asymptomatic No HAART 311 Asymptomatic HAART 1112 Asymptomatic HAART 1613 Unknown Unknown Unknown14 AIDS HAART 3

HAART, highly active antiretroviral therapy.

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these variables until the best model was determined.

Immunoglobulin levels were not included in the multivariate

analysis because they are not independent variables (ie,

depend on other variables such as CD4 cell count and HIV

viral load). After we successfully included all 3 variables (age,

sex, and viral load) in the logistic regression model, we tried

to add the dichotomous variable CD4 cell count (ie, high or

low CD4 count corresponding to a CD4 count ≥350 or

<350/µL [0.35 × 109 /L]) to the model. The resultant model

❚Table 5❚ with these 4 variables (age, sex, viral load, and CD4

cell count) proved to be better than the 3-variable model (age,

sex, and viral load) with a nonsignificant goodness-of-fit test

result (P = .3563). According to the final best model, younger

age, female sex, viral load, and CD4 cell count (≥350 vs

<350/µL [0.35 × 109 /L]) were associated with banding.

DiscussionAlthough most laboratory professionals are aware that a

large percentage of HIV+ patients may show striking poly-

clonal hypergammaglobulinemia and/or oligoclonal banding,

❚Table 4❚Distribution of Different Clinicopathologic CharacteristicsAmong 320 Patients With Banding (Monoclonal or Oligoclonal)and Without Bands in the Protein Electrophoresis Pattern*

Banding No Banding

Factor (n = 40) (n = 280) P

Mean age (y) 38.9 43.6 <.001†

Age (y) .067‡

<40 (n = 100) 18 (18.0) 82 (82.0)≥40 (n = 220) 22 (10.0) 198 (90.0)

Sex .011‡

Female (n = 67) 15 (22) 52 (78)Male (n = 253) 25 (9.9) 228 (90.1)

CD4 cell count/µL (×109 /L) .195‡

<350 (0.35) (n = 95) 8 (8) 87 (92)≥350 (0.35) (n = 225) 32 (14.2) 193 (85.8)

HIV viral load .002‡

Undetected (n = 145) 9 (6.2) 136 (93.8)Detected (n = 175) 31 (17.7) 144 (82.3)

Mean CD4 cell count/µL 570.5 (0.57) 556.2 (0.56) .797†

Mean log HIV viral load 3.34 2.69 .004†

(copies/mL)

* Data are given as number (percentage) unless otherwise indicated.† Independent samples t test.‡ χ2 test.

0

20

Undetected

Viral Load

No banding

Banding

P e r c e n t a g e

Detected

40

60

80

100

0

10

30

50

70

90

20

Female

Gender

No banding

Banding

P e r c e n t a g e

Male

40

60

80

100

A B

❚Figure 1❚ Percentage of banding and no banding on the protein electrophoresis patterns in patients with detected or

undetected viral loads (A) and female or male patients (B).

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we found the vast majority of electrophoretograms in this pop-

ulation to be visually unremarkable or to show only subtle

abnormalities. Estimates of the prevalence of monoclonal

bands in healthy populations vary, but one study found that

5% of a cohort of adults (with unknown HIV status) between

22 and 65 years of age showed 1 or more electrophoretically

homogeneous (presumably monoclonal) bands using a high-

resolution agarose gel technique.10 The reported prevalence of

monoclonal gammopathy of undetermined significance

(MGUS) in healthy (non-HIV+) subjects is between 1% and

2% and varies by age.11 A recent report noted that only 2% of

a series of more than 1,300 patients with MGUS were younger

than 50 years,11 and the overall male/female ratio was

1.19:1.12 Our findings, in which 4.4% of HIV+ patients had

monoclonal and 8.1% had oligoclonal bands, show higher

rates than the aforementioned findings. This confirms earlierstudies that have shown an increase in oligoclonal and mono-

clonal banding in HIV+ patients ❚Table 6❚.1,13-24 Many of the

prior studies involving HIV-infected persons have been rela-

tively small, with only 3 studies reporting data for more than

70 patients. There is considerable variability in the findings

reported, which is likely due to diverse methods used for iden-

tifying patients, variable sensitivity of the electrophoretic

methods, and interobserver variation in classification of elec-

trophoretic patterns.

Despite these factors, we can still draw some general con-

clusions from the literature. The reported prevalence of mono-

clonal bands in HIV+ patients ranges between 2.5% and 53%

and for oligoclonal banding, between 3% and 63%. Some

studies have grouped oligoclonal and monoclonal patterns

together, as we have, and the prevalence in these studies

ranges from 9% to 69% (Table 6). The reported prevalence of

oligoclonal bands in HIV+ patients may have decreased over

time, with 4 of 5 studies published in 1989 or before reporting

oligoclonal banding in more than 40% of patients, but 3 stud-

ies since 1990 have found oligoclonal banding in fewer than

40% of patients. Our finding of a 12% prevalence of oligo-

clonal or monoclonal bands in HIV+ patients is consistent

with this trend. We think that this decrease is probably real and

not an artifact of our study method. We used a high-resolution

semiautomated electrophoresis system that is in wide use in

clinical laboratories. In addition, this system has been report-

ed to be very sensitive for the detection of low-concentration

bands.25 Our findings confirm this high sensitivity because the

average concentration of the monoclonal bands we identified

was only 2.1% (1.85 g/L) of total protein, and the smallest

band we detected was only 0.3 g/L.

Elevated levels of immunoglobulins have been described

in patients with AIDS since at least 1984.26 Our findings con-

firm that a significant proportion (43%) of HIV+ patients have

elevations of the level of 1 or more immunoglobulins, usuallyIgG. The magnitude of the IgG elevation is modest in most

patients, but 10% of patients had IgG levels more than double

the upper limit of the reference range. By visual inspection of

the PEP, we interpreted only 6 cases to be hypergammaglobu-

linemic (these 6 cases had an average total IgG level of 2,651

❚Table 5❚Final Logistic Regression Model

95% ConfidenceInterval

Variable Odds Ratio Lower Upper P

Age* 1.06 1.02 1.11 .0163

Female sex 2.4 1.13 5.11 .0232Log viral load† 1.50 1.14 1.98 .0043CD4 cell count ≥350 2.71 1.09 6.75 .0327

vs <350/µL (0.35 × 109 /L)

* With each decreasing year of life.† With each increasing logarithmic viral load of 1.0.

❚Table 6❚Studies of Prevalence of Monoclonal and/or Oligoclonal Banding in AIDS/HIV+ Patients by Protein Electrophoresis

Oligoclonal Monoclonal Oligoclonal or

Study Year No. of Patients Banding (%) Banding (%) Monoclonal Banding (%)

Heriot et al1 1985 24 — 53 —Papadopoulos et al13 1985 42 61 8 69Sala et al14 1986 26 — 12 —Crapper et al15 1987 65 3 6 9Sala et al16 1987 55 — — 47Lefrere et al17 1987 243 — 2.5 —Papadopoulos and Costello18 1987 68 63 — —Taichman et al19 1988 44 43 — —Bratt et al20 1989 25 56 — —Amadori et al21 1990 60 15 — —Frankel et al22 1993 13 38 — —Lefrere et al23 1993 341 — 3.2 —Pontet et al24 1998 212 22 11 33Present study 2006 320 8 4 12

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mg/dL [26.51 g/L]). This reflects the fact that we were main-

ly looking for qualitatively abnormal bands (M proteins) and

were relatively conservative in what we interpreted as a poly-

clonal increase in staining in the γ region. Although protein

electrophoretograms can be quantitated by densitometry,

clearly, our visual impression was not as sensitive as the quan-

titative measurement.

A number of studies21,27-30 have demonstrated that oligo-

clonal and monoclonal bands and even paraproteins in cases

of multiple myeloma in HIV+ patients can be directed against

HIV antigen epitopes. Other studies have shown that on fur-

ther evaluation, even an apparently monoclonal paraprotein

band detected by PEP can often be shown to have more than

1 light chain type and reactivity against different HIV anti-

gens, suggesting that there is an exuberant polyclonal immune

response against HIV that may manifest as monoclonal or

oligoclonal banding.28,29 These findings, coupled with our

own observation that patients with elevated total IgG levels

were more likely to show oligoclonal or monoclonal bands,

support the hypothesis that these bands are more than likely

part of an immune response directed toward HIV. Given these

lines of evidence, it may make sense to consider oligoclonal

banding and low-concentration monoclonal bands in HIV+

patients to be part of the same spectrum of immune response.

This is an important point for laboratory professionals

and clinicians. There is evidence of a slightly increased risk of

multiple myeloma in HIV+ patients,31-34 and there have been

a number of case reports of unequivocal multiple myeloma

occurring in HIV+ patients. Amara et al9 reported that 28% of

their HIV+ patients with monoclonal gammopathy developeda malignancy (usually a B-cell/plasma cell malignancy) after

a mean follow-up of only 21 months. However, our findings

support the contention that most of the single, apparently

monoclonal, bands seen on PEP are not of a character that is

likely to be associated with multiple myeloma or other signif-

icant systemic plasma cell dyscrasia, but are more typical of

what might be seen with MGUS. Only 1 monoclonal band

was accompanied by a concomitant decrease in the other

immunoglobulins, and none of the bands was present in high

concentration (all were <5% of total protein). It is possible

that the cases in which we identified only a single band wouldhave shown additional bands if analyzed using more sensitive

techniques than are typically used in a clinical laboratory.

Although protein electrophoresis may not be routinely

ordered for HIV+ patients (ordered approximately in 9% of

the patients in our institution), if a PEP is performed and a

low-concentration monoclonal band is seen, it would be wise

to consider monitoring the PEP result over time.

Our multivariate analysis identified 4 factors that were

significantly associated with banding (monoclonal or oligo-

clonal): increased viral load, female sex, younger age, and

higher CD4 cell counts. Although these 4 factors can be seen

in patients who are newly diagnosed and have not yet received

HAART, our findings do not support that possibility. In that

regard, the overwhelming majority of patients (11/12) with

monoclonal banding were receiving HAART therapy and had

already had HIV infection for a mean duration of 8.0 years.

These results are consistent with the hypothesis that as the HIV

viral load increases, the host B cells respond by making more

immunoglobulins (probably directed specifically at HIV epi-

topes), which can be detected on PEP as bands (monoclonal or

oligoclonal). Our findings are consonant with those of Redgrave

and colleagues,35 who reported that aviremic HIV-infected

patients receiving HAART have lower plasma levels of IgG and

IgA than viremic HIV-infected patients. The fact that patients

with CD4 cell counts of less than 350/µL (0.35 × 109 /L) were

less likely to show banding on PEP is also consistent with the

central role of CD4 cells in promoting terminal differentiation,

antibody secretion, and immunoglobulin isotype switching in

activated B cells. The increased banding associated with female

sex is unclear but may be related to the increased incidence of

autoimmune diseases in female patients.36,37

Our study of immunoglobulins and protein electrophoret-

ic patterns in 320 HIV+ patients showed an increased preva-

lence of oligoclonal or monoclonal bands. The prevalence of

HIV-related banding seems to be lower than what has been

previously reported, perhaps in part owing to the more effec-

tive antiretroviral therapies that are currently available. HIV+

patients who were younger and female, had higher HIV viral

loads, and had CD4 cell counts more than 350/µL (0.35 ×

109 /L) were more likely to have an abnormal banding pattern

detected on PEP. Although HIV+ patients may be at slightlyhigher risk of developing multiple myeloma, all of the abnor-

mal PEP patterns we identified were oligoclonal or low-con-

centration monoclonal bands.

From the 1 Division of Hematology Oncology and 3 Department of

Pathology, Beth Israel Deaconess Medical Center and Harvard

Medical School, Boston, MA; and 2 Department of Pathology,

Baystate Medical Center, Tufts University School of Medicine,

Springfield, MA.

Address reprint requests to Dr Dezube: Beth Israel

Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215.

Acknowledgments: We acknowledge the invaluable assistanceof Shiva Gautam, PhD, with statistical analysis and of Carol Sklar

for technical laboratory assistance in this study.

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2. Le Carrer D. Serum Protein Electrophoresis and Immunofixation:Illustrated Interpretations. Washington, DC: AmericanAssociation for Clinical Chemistry; 1994:94-108.

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