Human Antibodies

Cloning Human Antibodies

Immune responses are among the most effective protection mechanisms against diseases, and antibodies can be effective against neurodegeneration. ISAB integrates a acoustic-dispensing platform (40,000 ELISAs/day) with clinical biobank samples. The goal is to identify disease-relevant signatures, stratify patients using machine learning, and clone protective human antibodies from high-affinity responders.

Large-scale seroepidemiology connects tau autoimmunity and to kidney disease

Using our high-throughput acoustic-dispensing microELISA pipeline, we screened large cohorts of human plasma for naturally occurring IgG autoantibodies against the microtubule-binding domain of tau (MTBD-tau). We then linked seroreactivity to clinical diagnoses and laboratory parameters in a hypothesis-free manner.

What we did

Quantified anti–MTBD-tau IgG using miniaturized, automated microELISAs with dilution-curve quality control.
Validated antibody specificity using competition assays and controls for nonspecific binding.
Purified tau-reactive antibodies from selected donors and tested functional effects on tau aggregation and assay performance.
Performed large-scale association analyses with ICD-10 codes and routine clinical laboratory parameters.

Key findings

Natural anti-tau antibodies are common and enriched in hospital cohorts compared with healthy donors.
High specificity: the autoreactive response is directed against tau with limited polyreactivity.
Functional impact: endogenous antibodies can inhibit tau aggregation and interfere with tau immunoassays.
No robust association with neurological disease, including Alzheimer's disease.
Strong association with nephro-urological pathology, supported by clinical diagnoses and laboratory markers.

Why this matters: These results extend tau biology beyond the nervous system and have implications for plasma tau biomarker interpretation and for tau-directed immunomodulatory strategies. As a cross-sectional study, the data do not establish causality.

Study overview and seroprevalence of anti-MTBD-tau antibodies — **Figure 1.** Study design, quality control workflow, and seroprevalence of anti-MTBD-tau IgG in hospital patients versus healthy donors.

Functional effects of endogenous anti-tau antibodies on tau aggregation and detection — **Figure 3.** Purified endogenous anti-tau antibodies inhibit tau aggregation in vitro and, depending on epitope specificity, interfere with tau immunoassays.

Lack of association between tau autoreactivity and neurological disease — **Figure 5.** Neurological disease categories, including Alzheimer's disease, show no robust association with anti-tau autoreactivity.

Association of tau autoimmunity with kidney and urinary disorders — **Figure 6.** Hypothesis-free association analysis identifies kidney and urinary disorders as the strongest clinical correlates of tau autoreactivity, supported by routine laboratory parameters.

Reference: MagalhÃ£es AD et al. Large-scale seroepidemiology uncovers nephro-urological pathologies in persons with tau autoimmunity. PLOS Biology.