Identification and monitoring of acid hydrolysis products of immunoglobulin heavy chains

A method for quantifying IgG heavy chain acid hydrolysis products in a sample, the method comprising:

• providing a sample comprising immunoglobulins;
• immunopurifying IgG immunoglobulins from the sample;
• subjecting the IgG immunoglobulins to an acid to hydrolyze the IgG immunoglobulins;
• subjecting the hydrolyzed IgG immunoglobulins to a mass spectrometry technique to obtain a mass spectrum of the sample;
• identifying the presence of IgG heavy chain acid hydrolysis products based on the multiply charged ion peaks in the spectrum;
• and
• converting the peak area of the identified peaks to a molecular mass to quantify the IgG heavy chain acid hydrolysis products in the sample.

A method for diagnosing a disorder in a patient, wherein said disorder is associated with altered production of IgG immunoglobulins, the method comprising:

• providing a sample comprising immunoglobulins;
• immunopurifying IgG immunoglobulins from the sample;
• subjecting the IgG immunoglobulins to an acid to hydrolyze the IgG immunoglobulins;
• subjecting the hydrolyzed IgG immunoglobulins to a mass spectrometry technique to obtain a mass spectrum of the sample;
• identifying the presence of IgG heavy chain acid hydrolysis products based on the multiply charged ion peaks in the spectrum;
• converting the peak area of the identified peaks to a molecular mass to quantify the IgG heavy chain acid hydrolysis products in the sample;
• comparing the quantity of IgG heavy chain acid hydrolysis products to a reference value;
• and
• identifying the patient as having a disorder associated with altered production of IgG immunoglobulin when the quantity of IgG heavy chain acid hydrolysis products in the sample is increased or decreased relative to the reference value.

A method for treating a disorder in a patient, wherein said disorder is associated with altered production of IgG immunoglobulins, the method comprising:

• identifying said patient as having said disorder, said identifying comprising:
• providing a sample comprising immunoglobulins;
• immunopurifying IgG immunoglobulins from the sample;
• subjecting the IgG immunoglobulins to an acid to hydrolyze the IgG immunoglobulins;
• subjecting the hydrolyzed IgG immunoglobulins to a mass spectrometry technique to obtain a mass spectrum of the sample;
• identifying the presence of IgG heavy chain acid hydrolysis products based on the multiply charged ion peaks in the spectrum;
• converting the peak area of the identified peaks to a molecular mass to quantify the IgG heavy chain acid hydrolysis products in the sample;
• comparing the quantity of IgG heavy chain acid hydrolysis products to a reference value;
• and
• identifying the patient as having a disorder associated with altered production of IgG immunoglobulin when the quantity of IgG heavy chain acid hydrolysis products in the sample is increased or decreased relative to the reference value;
• and
• administering to said patient a therapeutic agent to treat said disorder.

A method of monitoring a treatment of a disorder in a patient, wherein said disorder is associated with altered production of IgG immunoglobulins, the method comprising:

• providing an initial sample comprising immunoglobulins from the patient, wherein said initial sample is obtained from the patient prior to the treatment;
• providing one or more secondary samples comprising immunoglobulins, wherein said one or more secondary samples are obtained from the patient during the treatment, after the treatment, or both;
• immunopurifying IgG immunoglobulins from the samples;
• subjecting the IgG immunoglobulins to an acid to hydrolyze the IgG immunoglobulins;
• subjecting the hydrolyzed IgG immunoglobulins to a mass spectrometry technique to obtain a mass spectrum of the samples;
• identifying the presence of IgG heavy chain acid hydrolysis products in said samples based on the multiply charged ion peaks in the spectrum;
• converting the peak area of the identified peaks to a molecular mass to quantify the IgG heavy chain acid hydrolysis products in the samples;
• and
• comparing the quantity of the IgG heavy chain acid hydrolysis products from the initial sample and the one or more secondary samples.