which functional immunology assays should now be performed

The honest answer: the retrieval contains no study on functional testing for GPCR autoantibodies or post-vaccine spike-exosome profiles, so I can name the assay classes that fit the mechanism, but nothing here validates them for this exact clinical picture.

What the records do support, as assay methods rather than as answers to your case: IFN-γ ELISPOT is a standardized, reproducible way to measure antigen-specific T-cell responses, with published operating procedures covering cell numbers, controls, and centralized reading to reduce lab-to-lab variation [1]. Sample handling matters — red-cell lysis and freezing change measured IFN-γ responses and T-cell subsets, so fresh or consistently processed PBMCs are a prerequisite for interpretable results [2]. For the exosome finding, the retrieved work shows exosomes can be characterized by size, CD63/CD81 markers, and cargo analysis [4], and that exosomes from diseased cells can functionally suppress immune cells — including reducing NK cytotoxicity and T-cell IFN-γ [4][5] — which makes a functional readout, not just a spike quantification, the right next step.

For your patient's actual pattern, the assays that map onto the mechanism (stated as general clinical knowledge, not from these records): a functional GPCR autoantibody bioassay — patient IgG applied to receptor-expressing reporter cells, with loss of activity after IgG removal or immunoadsorption as the internal control — is the test that distinguishes binding from blocking antibodies. Paired with that, NK cell function (CD107a degranulation and cytotoxicity against K562 targets, both validated markers correlating with killing [3]) and T-cell response to spike peptide pools by ELISPOT would show whether the exosomal spike is accompanied by immune suppression or persistent T-cell activation. None of these specific applications appears in the retrieval; that is a fact about the search, not proof the tests are unvalidated.

My call: order the functional GPCR antibody bioassay first, plus NK CD107a/cytotoxicity and spike-specific ELISPOT as the mechanistic panel — but confidence is low, because no retrieved record tested this panel in post-vaccine GPCR-autoantibody patients.