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400 - 1705 Corporate Drive Norcross, GA 30093 Telephone: (800) 835-6497 Fax: (770) 446-8511 www.sebia-usa.comEditors: Lydia Dodson-Lehrer, MBA, M.T. (ASCP) & Bonny Champagne, M.T. (ASCP)

issue 3 vol. 4

2003

C l e a r l y S u p e r i o

Aut

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The most sensitivoligoclonal immunfocusing.I

Investigators anaby IEF and showedclinically definite MIgG bands in their

Electrophoresis of(CSF), in order to banding, is one oflaboratory tests inpatient suspectedsclerosis (MS). Asgreat percentage exhibit oligoclonacourse of the diseearly in the diseasthrough remission

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1 Andersson M, Alvarez-Cerrneno J, et al. Cerebrospinal fluid in the diagnosis of multiple sclerosis: a consensus report.Journal of Neurology, Neurosurgery, and Psychiatry 1994 Aug; 57(8): 897-902.2 Mehta, PD. Diagnostic Usefulness of Cerebrospinal Fluid in Multiple Sclerosis. Crit Rev Clin Lab Sci. 1991; 28(3): 233-51.3 Mehta, PD, Patrick BA, Black J. Comparison of oligoclonal immunoglobulin G bands in multiple sclerosis cerebrospinalfluid by immunoblotting and immunofixation. Electrophoresis. 1988 Mar; 9(3): 126-8.

2% per year and it was related to the amount of monoclonal protein found at the initial diagnosis of MGUS (e.g., at theinitial 0.5 g/dL and 3 g/dL, the risk was about 0.6% and 3% per year, respectively). Interestingly, the amount ofmonoclonal protein at diagnosis of multiple myeloma is not a predictive factor of the outcome of the disease. Patientswith monoclonal IgA and IgM had an increased risk of progression compared to monoclonal IgG. More recent findingsindicate that biclonal MGUS have a higher risk of progression than previously thought. In only 2% of the patients, theinitial small monoclonal protein (with a measurable spike) disappeared.

Opposite conclusions were drawn whether or not detectable Bence Jones proteinuria is a risk factor for theprogression. Age, sex, the presence of connective tissue disorder, viral hepatitis, solid tumors, iatrogenicimmunosuppression, serum albumin and 2-microglobulin did not appear to be risk factors. However, normal rangeconcentrations of the latter two proteins as well as of CRP, 1-antitrypsin and thymidine kinase are believed to beprerequisite for MGUS classification. The reduction of polyclonal immunoglobulin background (hypo-gammaglobulinemia), although a controversial risk factor for progression, must always be interpreted with caution. Itmight be the first laboratory indication of a lymphoproliferative disorder associated with limited or absent secretion of amonoclonal protein into serum, e.g., in li ght chain disease (LCD), amyloidosis, lymphoma, etc. The level of bonemarrow plasma cells (>10%) and in some studies hypo-gammaglobulinemia were identified as independent riskfactors requiring stricter monitoring of the MGUS patients.

From the patients who progressed into a malignant disorder, most developed multiple myeloma. Other notabledisorders were I gM lymphoma, primary amyloidosis, Waldenstrms macroglobulinemia and non-Hodgkins lymphoma.

The undisputed conclusion: since the benign nature of MGUS is generally impossible to ascertain, the patientsdiagnosed with MGUS should be monitored for the rest of their lives. Usually the first follow-up testing is suggested sixmonths after the initial diagnosis. If the monoclonal protein and other biochemical markers remain stable in theasymptomatic patient, next follow-up in one year seems to be sufficient.

There is still much to be learned about MGUS. The molecular and cellular changes in the progression of clonal cells toa malignant condition have not been clearly delineated. Structural chromosomal abnormalities and chromosomaltranslocations seem to occur early in the clonal development; however, none of these changes are specific for allMGUS. It is also unclear whether or not smoldering and indolent myeloma are the necessary or only occasionaltransitory stages in the progression of MGUS. Currently, there is still no way to tell whether the progression will happenand when or whether the clonal proliferation will stay arrested in the benign form.

If you are interested in receiving information concerning Sebias Hydragel Protein(155)or Hydragel

Immunofixation (156) assays, please circle the appropriate nu mber on the Reader Response Card or visit ourwebsite (http://www.sebia-usa.com/products/reagents.html).

Ask Borek

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References

Oligoclonal IgG Banding Detection: The Most Sensitive Method

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Ask Borek Customer FocusBy: Borek Janik, Ph.D.

Clinical and Scientific Affairs Manager

Inthe meantime, keepsendingin thosequestions. Youmay sendthemto me by mailat Sebia, 400-1705 CorporateDrive, Norcross, GA30093, attn. Ask Borek, by fax at 770-446-8511attentionAskBorek, orby e-mailat borek.janik@sebia-usa.com. Whichevermethod youchoose, includeyour name, laboratory nameand phonenumber shouldI havequestions foryou.

LIFE IN THE LABORATORY

By: Josie C. Roberts, MT (ASCP), NCA

Life to save, life to lose, new life to bring

Into the world of the laboratory

For to adequately fit into its space

Education to fulfill obtained

In the hospital, clinic, doctors office

Night and day, all hours, all seasons

Tests on injured, sick, diseased

Help maintain, evaluate, educate

Ever current procedure, protection

Light or heavy chain, alpha, gamma, or beta

Areas for culture, coag, hematology, chemistry

Bilirubin, blood counts, B-cell or T-cell

Online results relayed to chart

Results confirmed, rule out, or monitor

As protime, fibrinogen, urinalysis

Total protein, cardiac enzyme

On blood, urine, body fluids

Ready to rush to the task

Yearly professionals nationwide assemble to examine, evaluate, educate

LIFE IN THE LABORATORYwas submitted to Sebia by Ms. Josie C. Roberts at this years AACCPhiladelphia, PA. Josie has been a laboratory scientist for 36 years and finds the field just as etoday as it was in the very beginning. Josie is employed at Saint Francis Medical Center in MoDuring her 21 years at Saint Francis Medical Center, Josie has worked in the microbiology lab recently, the hematology lab. On behalf of all the Sebia staff, thank you for your time and creatwriting and submitting this truly wonderful laboratory poem!

MGUS always has been a very populartopic when it comes to interpretation ofweak and unusual immunofixationpatterns when their diagnosticsignificance is far from obvious.Sometimes I feel the MGUS categoryis abused as it serves as a garbagedisposal for hazy results. Such asituation is not due to insufficient interestin resolving the mystery of MGUS.

The classification and diagnosticsignificance of the monoclonalgammopathies that are grouped underMGUS is a frequent subject ofdiscussions by the experts and matter ofconfusion to others. Not enough isknown about the cause of MGUS, theirorigin and further development. MGUS,also referred to as essential monoclonalgammopathy, is typically associated withlow levels of a monoclonal proteinproduced by a single clone of plasmacells that appear to be in a benign orpre-neoplastic state. Some argue thatconsidering MGUS a benign conditionmight be misrepresentation. The earlytrend to amplify the M component mightbe slow but clonal evolution to overt MMor kindred B cell malignancies doesoccur in 1-2% cases per year. Eventually,given enough time some believe, allcases of MGUS would convert. The mostintriguing question thus remains

unanswered, whether or not MGUS willstay arrested in the benign state or willprogress to an aggressive, malignantstate (either directly or via smolderingmyeloma), and what are the molecularand cellular changes causing andaccompanying such progression.Although such a state of uncertainty isnot favored by those who prefer blackand white interpretation of laboratoryresults, this is exactly what MGUS is -amonoclonal gammopathy ofundetermined significance.

The criteria for classification of MGUSproposed in the past, namely the cutoffconcentrations of monoclonal proteins inserum and urine, differed somewhat fromstudy-to-study. The InternationalMyeloma Working Group has reviewedthe criteria for diagnosis andclassification with the aim of producingeasy to use definitions based onroutinely used investigations. The criteriawere presented at the 9th InternationalWorkshop on Multiple Myeloma, May2003, in Salamanca, Spain. According tothe consensus, a patient with MGUS ischaracterized as follows:

low levels of monoclonal proteinin serum < 3g/dL (