Abstract
Recently, a mass spectrometry-based approach was introduced to directly assess the IgG1 immunoglobulin clonal repertoires in plasma. Here we expanded upon this approach by describing a mass spectrometry-based technique to assess specifically the clonal repertoire of another important class of immunoglobulin molecules, IgA1, and show it is efficiently and robustly applicable to either milk or plasma samples. Focusing on two individual healthy donors, whose milk was sampled longitudinally during the first 16 weeks of lactation, we demonstrate that the total repertoire of milk sIgA1 is dominated by only 50-500 clones, even though the human body theoretically can generate several orders of magnitude more clones. We show that in each donor the sIgA1 repertoire only changes marginally and quite gradually over the monitored 16-week period of lactation. Furthermore, the observed overlap in clonal repertoires between the two individual donors is close to non-existent. Mothers provide protection to their newborn infants directly by the transfer of antibodies via breastfeeding. The approach introduced here, can be used to visualize the clonal repertoire transferred from mother to infant and to detect changes in-time in that repertoire adapting to changes in maternal physiology.
Highlights
A large part (~35%) of the proteins in our blood are immunoglobulins (Ig)
The method was first optimized using a recombinant monomeric IgA1, and subsequently we show that the method works well on repertoires of sIgA1 from human milk and IgA1 repertoires purified from plasma
We introduce a fast and sensitive approach for analyzing and monitoring IgA1 clonal repertoires from complex biofluids, Monitoring IgA Repertoires in Bodyfluids B. Such as human milk and plasma, revealing that the method is unbiased towards monomeric IgA1 (mIgA1) or hetero-oligomeric sIgA1s
Summary
A large part (~35%) of the proteins in our blood are immunoglobulins (Ig). These immunoglobulins, or antibodies, are used by our immune system to identify and neutralize pathogenic bacteria and viruses among others [1]. In human plasma (i.e., blood from which cells have been depleted) three dominant classes of immunoglobulins are present, namely IgG, IgA and IgM. Their concentration levels differ per individual but are generally highest for IgG 8.3-11.2 g/L, and somewhat lower for IgA 1.6-2.8 g/L and IgM 0.6-1.2 g/L [2]. For human IgG, four sub-classes can be distinguished, IgG1, IgG2, IgG3 and IgG4, and for human IgA two sub-classes co-exist: IgA1 and IgA2
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