IgG, IgA, IgM, IgD Assays
The quantification of serum immunoglobulins is a vital first-line test in the investigation of Primary Immunodeficiency (PID).1 The results are often the basis for further investigative testing such as antibody function. IgG, IgA and IgM concentrations can be measured reliably by a wide range of laboratory assays and are a useful screening method for the detection of agammaglobulinaemia and hypogammaglobulinaemia.
Selective IgA deficiency is the most common antibody deficiency. It can be defined as a serum IgA level of less than 0.07g/L (and normal IgG and IgM levels) in a patient older than 4 years.2,3
All Binding Site immunoglobulin assays are calibrated to the International Reference Preparation ERM®-DA470k/IFCC (DA470k; Institute for Reference Materials and Management). This ensures that sample results remain accurate and consistent.
The quantitation of IgD in serum samples is an important part in the diagnosis and monitoring of PID. Hyper-IgD syndrome has been described as a consideration in phagocyte deficiencies4 and IgD levels are also increased in periodic fever syndrome.5
Immunoglobulins (IgG, IgA, IgM, IgD) – Product Information
Immunoglobulins (IgG, IgA, IgM, IgD) – Product InformationSPAplus Assays
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Description
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Pack
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Code
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IgG SPAplus kit
Range: 1650 – 35000 mg/L Sensitivity: 165 mg/L
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100 test
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NK004.S
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IgA SPAplus kit
Range: 200 – 7000 mg/L Sensitivity: 200 mg/L
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100 test
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NK010.S
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IgM SPAplus kit
Range: 200 – 7500 mg/L Sensitivity: 100 mg/L
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100 test
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NK012.S
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IgD SPAplus Latex kit
Range: 7-210 mg/L Sensitivity: 7mg/L
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100 test
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LK013.S
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Assays for MININEPH™™ and MININEPHplus™
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Description
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Pack
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Code
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IgG MININEPH™ kit
Range: 2000 – 25000 mg/L
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50 test
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ZK004.R
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IgG-LL MININEPH™ kit*
Range: 10 – 168 mg/L
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50 test
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ZK004.LL
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IgA MININEPH™ kit
Range: 370 – 5940 mg/L
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50 test
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ZK010.R
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IgM MININEPH™ kit
Range: 250 – 4000 mg/L
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50 test
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ZK012.R
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Other assays are available on the MININEPH™ and MININEPH™PLUS
Siemens BN™II Assay
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Description
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Pack
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Code
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IgD BN™II Latex kit
Range: 130 – 4150 mg/L
Range: 6.5 – 207.5 mg/L
Sensitivity: 1.3 mg/L
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2 x 50 test
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LK013.T
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Radial Immunodiffusion
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Description
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Pack
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Code
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IgG RID kit – NL |
3 plate kit |
RN004.3 |
| IgG RID kit – ML* Range: 18 – 180 mg/L |
3 plate kit | RL004.3 |
| Nanorid™ IgG kit – UL* Range: 0.45 – 4.5 mg/L |
3 plate kit | GL004.3 |
| IgM RID kit – NL Range: 265 – 2650 mg/L |
3 plate kit | RN012.3 |
|
Nanorid™ IgM kit – ML* |
3 plate kit | GM012.3 |
| Nanorid™ IgM kit – UL Range: 0.35 – 3.5 mg/L |
3 plate kit | GL012.3 |
| IgG, IgA, IgM COMBI RID kit – NL One plate each of IgG, IgA & IgM |
3 plate kit | RK002 |
| IgA RID kit – NL Range: 545 – 5450 mg/L |
3 plate kit | RN010.3 |
| IgA RID kit – ML* Range: 8.5 – 85 mg/L |
3 plate kit | RL010.3 |
| Nanorid™ IgA RID kit – UL* Range: 0.43 – 4.3 mg/L |
3 plate kit | GL010.3 |
| Secretory IgA RID kit – NL* Range: 45 - 450 mg/L |
3 plate kit | RN148.3 |
| IgD RID kit – NL Range:8.5-85 mg/L |
3 plate kit | RN013.3 |
* For research use only
Binding Site SPAplus™ Analyser
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Description
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Pack
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Code
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IgG1 SPAPLUS kit
Range: 1500-36000 mg/L
Sensitivity: 150 mg/L
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100 test
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NK006.S
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IgG2 SPAPLUS kit
Range: 200-7000 mg/L
Sensitivity: 20 mg/L
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100 test
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NK007.S
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IgG3 SPAPLUS Latex kit
Range: 55-1000 mg/L
Sensitivity: 5.5 mg/L
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100 test
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LK008.S
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IgG4 SPAPLUS Latex kit
Range: 30-850 mg/L
Sensitivity: 3 mg/L
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100 test
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LK009.S
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IgG SPAPLUS kit
Range: 1650-35000 mg/L
Sensitivity: 165 mg/L
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100 test
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NK004.S
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Siemens (Dade-Behring) BN™II
An alternative to the pre-programmed protocol must be selected to run these assays. Full details are provided in the product inserts.
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Description
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Pack
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Code
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BN™II Latex COMBI kit
(Latex IgG3 & IgG4, non-latex IgG1 & IgG2)
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2 x 48 test
2 x 40 test
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LK001.TB
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IgG1 BN™II kit
Range: 1310 - 42000 mg/L
Sensitivity: 66 mg/L
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4 x 40 test
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NK006.TB
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IgG2 BN™II kit
Range: 313 - 10000 mg/L
Sensitivity: 78 mg/L
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4 x 40 test
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NK007.TB
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IgG3 BN™II Latex kit
Range: 175 - 5600 mg/L
Sensitivity: 44 mg/L
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4 x 48 test
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LK008.TB
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IgG4 BN™II Latex kit
Range: 38 - 613 mg/L
Sensitivity: 1.9 mg/L
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4 x 48 test
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LK009.TB
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These assays use the pre-programmed parameters on the BN™II and do not incorporate latex enhanced reagents.
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Description
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Pack
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Code
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BN™II COMBI kit
(IgG1, IgG2, IgG3, IgG4)
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4 x 40 test
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NK001.T
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IgG1 BN™II kit
Range: 1310 - 42000 mg/L
Sensitivity: 66 mg/L
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4 x 40 test
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NK006.T
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IgG2 BN™II kit
Range: 313 - 10000 mg/L
Sensitivity: 78 mg/L
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4 x 40 test
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NK007.T
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IgG3 BN™II kit
Range: 175 - 5600 mg/L
Sensitivity: 44 mg/L
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4 x 40 test
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NK008.T
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IgG4 BN™II kit
Range: 120 - 3840 mg/L
Sensitivity: 30 mg/L
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4 x 40 test
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NK009.T
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Siemens (Dade-Behring) BN ProSpec® kits
In order to run Binding Site reagents on the BN ProSpec® it is necessary to open specific channels on the analyser and this may require the assistance of a Siemens engineer. Please contact us (Link to Contact) for further information.
| Description | Pack | Code |
| BN ProSpec® COMBI kit Non-latex IgG1 and IgG2 Latex IgG3 and IgG4 |
|
LK001.P |
| IgG1 BN ProSpec® kit Range 2625 - 84000 Sensitivity 131 |
4 x 40 test | NK006.P |
| IgG2 BN ProSpec® kit Range 613 - 19600 Sensitivity 153 |
4 x 40 test | NK007.P |
| IgG3 Latex BN ProSpec® kit Range 55 - 875 Sensitivity 2.7 |
4 x 48 test | LK008.P |
| IgG4 BN ProSpec® kit Range 38 - 613 Sensitivity 1.9 |
4 x 48 test | LK009.P |
Beckman Coulter IMMAGE®
These kits require the user to set up a user-defined reagent (UDR) for each assay.
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Description
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Pack
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Code
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IgG1 Beckman IMMAGE® kit
Range: 750 - 20000 mg/L
Sensitivity: 150 mg/L
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58 test
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NK006.IM
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IgG2 Beckman IMMAGE® kit
Range: 486 - 13125 mg/L
Sensitivity: 97 mg/L
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58 test
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NK007.IM
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IgG3 Beckman IMMAGE® Latex kit
Range: 100 - 2000 mg/L
Sensitivity: 10 mg/L
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58 test
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LK008.IM
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IgG4 Beckman IMMAGE® Latex kit
Range: 73 - 1500 mg/L
Sensitivity: 7.3 mg/L
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58 test
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LK009.IM
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Beckman Coulter AU®
A reaction accelerator for the latex assays is included.
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Description
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Pack
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Code
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IgG1 AU® kit
Range: 1500 - 40000
Sensitivity: 150
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100 test
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NK006.AU
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IgG2 AU® kit
Range: 486 - 13125 mg/L
Sensitivity: 97 mg/L
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100 test
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NK007.AU
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IgG3 AU® Latex kit
Range: 78 - 1250 mg/L
Sensitivity: 15.6 mg/L
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100 test
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LK008.AU
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IgG4 AU® Latex kit
Range: 20 - 750 mg/L
Sensitivity: 4 mg/L
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100 test
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LK009.AU
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Roche cobas® 6000 kits
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Description |
Pack |
Code |
| IgG1 cobas® 6000 kit Range: 1000-20000 mg/L Sensitivity: 333.3 mg/L |
100 test | NK006.CB |
| IgG2 cobas® 6000 kit Range: 600 - 10000 mg/L Sensitivity: 60 mg/L |
100 test | NK007.CB |
| IgG3 cobas® 6000 kit Range: 70 - 1312mg/L Sensitivity: 14 mg/L |
100 test | LK008.CB |
| IgG4 cobas® 6000 kit Range: 67.5 - 810 mg/L Sensitivity: 9 mg/L |
100 test | LK009.CB |
Roche Modular P / Hitachi
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Description
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Pack
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Code
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Modular P / Hitachi COMBI kit (Latex IgG3 & IgG4, non-latex IgG1, IgG2 & IgG)
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5 x 45 test
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LK001.H
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IgG1 Modular P / Hitachi kit
Range: 1000 - 20000 mg/L
Sensitivity: 330 mg/L
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4 x 45 test
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NK006.H
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IgG2 Modular P / Hitachi kit
Range: 600 - 10000 mg/L
Sensitivity: 60 mg/L
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4 x 45 test
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NK007.H
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IgG3 Latex Modular P / Hitachi kit
Range: 20 - 750 mg/L
Sensitivity: 7 mg/L
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4 x 45 test
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LK008.H
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IgG4 Latex Modular P / Hitachi kit
Range: 67.5 - 810 mg/L
Sensitivity: 9 mg/L
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4 x 45 test
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LK009.H
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The IgG subclass kits above have been developed for use on the following Roche / Hitachi analysers:
- Roche / Hitachi Modular P
- Hitachi 911
- Hitachi 912
- Hitachi 917
Radial Immunodiffusion
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Description
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Pack
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Code
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IgG Subclass RID COMBI kit – SD
One plate each of IgG1, IgG2, IgG3, IgG4 |
4 plate kit
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RK021
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IgG1 - SD RID kit
Range: 1400 - 14000 mg/L
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3 plate kit
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RN106.3
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IgG2 - SD RID kit
Range: 800 - 8000 mg/L
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3 plate kit
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RN107.3
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IgG3 - SD RID kit
Range: 120 - 1200 mg/L
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3 plate kit
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RN108.3
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IgG4 - SD RID kit
Range: 50 - 500 mg/L
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3 plate kit
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RN109.3
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MININEPH™ and MININEPHplus™
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Description
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Pack
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Code
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IgG1 MININEPH™ kit
Range: 1440 - 23000 mg/L
Sensitivity: 665 mg/L
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10 test
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ZK006.R
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IgG2 MININEPH™ kit
Range: 802 - 9625 mg/L
Sensitivity: 350 mg/L
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10 test
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ZK007.R
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IgG3 MININEPH™ Latex kit
Range: 153 - 2450 mg/L
Sensitivity: 153 mg/L
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2 x 5 test
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ZK008.L.R
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IgG4 MININEPH™ Latex kit
Range: 53 - 847 mg/L
Sensitivity: 2.2 mg/L
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2 x 5 test
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ZK009.L.R
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IgG subclass serum concentrations in healthy individuals vary with age, sex, race, Gm allotype and exposure to acute and chronic infections. When developing assays to measure IgG subclasses it is necessary to consider all these factors to ensure that the assays will meet clinical requirements in terms of sensitivity, specificity, reproducibility and quality of performance.
High Specificity IgG subclass antisera
Monoclonal antibodies are known to be highly specific for the target antigen however they may exhibit an allotype bias. This could lead to non-detection of a deficiency or reporting of a false deficiency. High quality polyclonal antisera with no IgG subclass cross-reactivity is therefore more suitable for the reliable measurement of subclass concentrations. Binding Site assays utilise highly specific, affinity-purified, polyclonal antisera raised in sheep using patented technology.
Standardisation for accurate and consistent measurement
Calibration of an assay against an internationally recognised reference preparation ensures that sample results remain accurate and consistent.
In 1997 Carr-Smith et al. assigned IgG subclass values to the international serum protein reference material CRM4706 which is the most commonly used reference material for commercial IgG assays. All Binding Site IgG subclass assays were subsequently calibrated against CRM470. Conversion factors are available for customers wishing to compare results with those obtained in assays calibrated against the earlier reference material WHO67/97 (no longer available).
As supplies of CRM470 run low, a new international reference material, ERM®-DA470k/IFCC (DA470k; Institute for Reference Materials and Management), has been produced. Binding Site assays have been shown to give accurate results when evaluated against this material.
Summary of assignment verification results obtained with CRM470 and DA470k on a number of analysers. Data was presented in a poster at The American Society of Clinical Chemists meeting, 2009, Chicago.7
Quality control and quality assurance
As the market leader in IgG subclass assays, Binding Site is acutely aware of the need for good quality control. Our laboratories are ISO9001:2008, ISO13485:2003 and FDA certified, and we participate in several external quality assurance schemes. We also offer customers the opportunity to participate in our own IMMPROVE™ Subclass Quality Assurance Scheme.
Quality control procedures for all our IgG subclass products include extensive checking against internal reference materials and CRM470. Kits are CE marked for the majority of European countries, FDA cleared and have a minimum shelf life of 12 months from date of manufacture.
Measurement of IgG subclass levels may be used as an aid in the diagnosis of primary immunodeficiency (PID), together with vaccine response tests.
Binding Site SPAplus Analyser
| Description | Pack | Code |
| IgA1 SPAplus kit Range 300 – 6000 mg/L Sensitivity 30 mg/L |
50 test | NK087.S |
| IgA2 SPAplus kit Range 50 – 1250 mg/L Sensitivity 5.0 mg/L |
50 test | LK088.S |
Radial Immunodiffusion (RID)
| Description | Pack | Code |
| IgA subclass RID COMBI kit IgA1 Range: 640 – 6400 mg/L IgA2 Range: 50 – 500 mg/L |
4 plate kit | RK015 |
This IgA subclass RID kit has been developed for the quantitation of IgA subclasses in human serum and cerebrospinal fluid.
The COMBI kit contains 2 plates for each subclass as well as calibrators and controls.
Beckman Coulter IMMAGE®
| Description | Pack | Code |
| IgA1 Latex IMMAGE® kit Range: 355 – 6000 mg/L Sensitivity: 37 mg/L |
40 test | LK087.IM |
| IgA2 Latex IMMAGE® kit Range: 50 – 1250 mg/L Sensitivity: 5.5 mg/L |
40 test | LK088.IM |
Siemens BN™II
Instructions on how to set up these protocols are provided in the product inserts.
| Description | Pack | Code |
| IgA1 BN™II kit Range: 375 – 6000 mg/L Sensitivity: 94 mg/L |
40 test | NK087.1T |
| IgA2 Latex BN™II kit Range: 63 – 1000 mg/L Sensitivity: 3 mg/L |
40 test | LK088.1T |
| IgA subclass BN™II COMBI kit Latex IgA2 Non-latex IgA1 |
2 x 40 test | LK003.T |
IgA is responsible for mucosal immunity and is therefore the first line of defence for the majority of infections. Deficiencies in IgA subclasses or alterations in the IgA1/IgA2 ratio have been related to specific diseases, recurrent infections and anaphylactic transfusion reactions. Normal serum concentrations of both IgA subclasses may be very low therefore a sensitive, reproducible assay is essential, particularly for paediatric samples. Binding Site IgA subclass assays also utilise highly specific high affinity, polyclonal antisera and latex-enhanced reagents enable accurate quantitation to very low levels.
- Wood, P. Primary antibody deficiency syndromes. Ann Clin Biochem 2009; 46(Pt 2):99-108
- Bonilla, F. A, Bernstein, I. L. et al. Practice parameter for the diagnosis and management of primary immunodeficiency. Ann Allergy Asthma Immunol 2005;94(5 Suppl 1):S1-63
- Aghamohammadi, A., Lougaris,V. et al 2008. Predominantly Antibody Deficiencies, p. 97-130. In Rezaei, N, Aghamohammadi, A. and Notarangelo, L.D. (ed.) Primary immunodeficiency diseases, 5th ed. Springer-Verlag, Berlin, Germany. ISBN 978-3-540-78537-8
- De Vries, E. Patient-centred screening for primary immunodeficiency: a multi-stage diagnostic protocol designed for non-immunologists. Clin Exp Immunol 2006;145(2):204-14
- Vladutiu, A. O. Immunoglobulin D: properties, measurement, and clinical relevance. Clin Diagn Lab Immunol 2007;(2):131-40
- Carr-Smith, H. D, Overton, J and Bradwell, A. R. IgG subclass Value assignment to the protein reference preparation CRM470. AACC 1997 Abstract from Binding Site on request
- Williams, D. R, Wilson, C. I. and Carr-Smith, H.D. Assignment of IgG Subclass Values to the Protein Reference Preparation DA470k. Clin Chem 2009;55(6) Supplement:A132
BN™II is a trademark of Siemens Healthcare Diagnostics Inc.
BN ProSpec® is a registered trademark of Siemens Healthcare Diagnostics Inc.
IMMAGE® and AU® are registered trademarks of Beckman-Coulter Instruments Inc.
MININEPH™™ and IMMPROVE™ are trademarks of The Binding Site Group Ltd, Birmingham, UK.
