Hereditary Bisalbuminemia in Sjögren’s Syndrome and Rheumatoid Arthritis

Bisalbuminemia is rare finding of bifid albumin bands in serum electrophoresis. The protein abnormality can be sporadic and inherited. So far, this albumin variant was not found to cause or coexist with a specific pathology. This is a case of bisalbuminemia in 43-year-old female patient with a past medical history of Rheumatoid Arthritis (RA) and Sjogren’s Syndrome (SS). Similar electrophoresis findings were seen in two siblings of the patient. Rheumatology focused work-up of the family was negative. We could not find an association between this blood protein variant and the patient’s rheumatologic condition. Bisalbuminemia should not be a concern to the rheumatologist as it does not hint towards pathology.

An engineered human albumin enhances half-life and transmucosal delivery when fused to protein-based biologics

Needle-free uptake across mucosal barriers is a preferred route for delivery of biologics, but the efficiency of unassisted transmucosal transport is poor. To make administration and therapy efficient and convenient, strategies for the delivery of biologics must enhance both transcellular delivery and plasma half-life. We found that human albumin was transcytosed efficiently across polarized human epithelial cells by a mechanism that depends on the neonatal Fc receptor (FcRn). FcRn also transported immunoglobulin G, but twofold less than albumin. We therefore designed a human albumin variant, E505Q/T527M/K573P (QMP), with improved FcRn binding, resulting in enhanced transcellular transport upon intranasal delivery and extended plasma half-life of albumin in transgenic mice expressing human FcRn. When QMP was fused to recombinant activated coagulation factor VII, the half-life of the fusion molecule increased 3.6-fold compared with the wild-type human albumin fusion, without compromising the therapeutic properties of activated factor VII. Our findings highlight QMP as a suitable carrier of protein-based biologics that may enhance plasma half-life and delivery across mucosal barriers.

An inherited albumin variant with enhanced affinity for the Amerlex thyroxin-analog.

We describe two siblings with artefactually increased results for free thyroxin in serum as measured with the Amerlex analog method, despite normal thyroxin transport. The cause of the artefact is identified as a variant albumin with enhanced affinity for the Amerlex thyroxin-analog.

Albumin Cooperstown: a serum albumin variant with the same (313 Lys----Asn) mutation found in albumins in Italy and New Zealand.

Albumin Cooperstown is an electrophoretically fast genetic variant (alloalbumin) inherited in a family in New York State. To determine the structural change, we separated the alloalbumin from normal albumin A by "high-performance" liquid chromatography, reduced and carboxymethylated it, and cleaved it with CNBr. Isoelectric focusing showed that the substitution was in fragment CB4 (residues 299 to 329). The variant CNBr fragment from the albumin of two siblings was purified by liquid chromatography. Automated sequence analysis established the substitution of lysine-313 by asparagine (313 Lys----Asn), which corresponds to mutation of a single nucleotide base. The same substitution has recently been reported in albumin variants in Italy and New Zealand. This provides the first evidence for independent mutations at a single site within the structure of the mature albumin molecule. Because of the significance of albumin for study of protein evolution, clinical chemists are asked to be on the alert for cases of bisalbuminemia.