Why don’t we see immunogenicity with Gh?

[EnhanceDeezNutz]

Hey y’all, I was talking with a medical provider the other day and they mentioned that some biologics can cause an autoimmune response after taking them for a while. They mentioned that it was “mostly peptide based” medications that do this. Why do we never really hear about autoimmune reactions to gh, despite using it chronically and at high doses? Is it something to do with the 192 vs 191 amino acid count?

 

[psauce]

I have not tracked this down, but it's not immediately apparent to me that we don't see an immune response from exogenous GH.

So many people experience discomfort in their hands, feet, and joints as well as less specific aches and stiffness. I have never looking into whether we know if this is tied to an IgE response, or a more general inflammatory response like CRP, but it's widespread enough that it suggests a physiological response to exposure.

 

[EnhanceDeezNutz]

I have not tracked this down, but it's not immediately apparent to me that we don't see an immune response from exogenous GH.

So many people experience discomfort in their hands, feet, and joints as well as less specific aches and stiffness. I have never looking into whether we know if this is tied to an IgE response, or a more general inflammatory response like CRP, but it's widespread enough that it suggests a physiological response to exposure.

Oh ok, I hadn’t considered that idea before. Of course I’ve heard of the carpal tunnel like symptoms with Gh use, but I always assumed it was due to water retention. Maybe it IS water due in part to an immune response because of inflammatory cytokines. Interesting point!

 

[Type-IIx]

A "biologic" is a drug product that is derived from natural sources (e.g., human, animal, micro-organism). For example, (cadaver) pituitary-derived GH, that was used before the advent of the E. coli recombinant DNA (rDNA) manufacturing process to yield rhGH (and before too the 192AA Somatrem, not Somatropin, that was manufactured by an inclusion body technology rather than rDNA process, also associated with GH antibodies). Pituitary-derived GH was associated with Creutzfeldt-Jakob disease outbreaks.

The modern 191AA recombinant human growth hormone (rhGH) produced from an E. coli rDNA process is associated with very low or insignificant antigenicity. From a large sample clinical trial using 3 different products and measuring antigenicity (formation of GH antibodies)
* Group A: 1.4% antigenicity (rhGH [E. coli])
* Group B: 2.8% antigenicity (rhGH [E. coli])
* Group C: 8.5% antigenicity (rhGH [mammalian cell line])

You can see that rhGH as it exists now has a very low prevalence of clinically insignificant GH antibody formation or antigenicity.

It's just a clean process that yields a very pure product.

 

[Type-IIx]

Oh ok, I hadn’t considered that idea before. Of course I’ve heard of the carpal tunnel like symptoms with Gh use, but I always assumed it was due to water retention. Maybe it IS water due in part to an immune response because of inflammatory cytokines. Interesting point!

@psauce it's just acromegalic symptomology: carpal tunnel; arthralgia; fractures; bony overgrowth; osteoarthritis; soft-tissue swelling leading to nerve entrapment; diabetes; hypogonadism (reduced testosterone); sleep apnea; cardiac dysfunction including myocardial hypertrophy; and risk of various cancers and nonmalignant tumor growth.

 

[janoshik]

I think the main clinical concern with antibodies would be decrease of actual circulating GH, not various noticeable side effects, especially such as those mentioned here. What do you think, @Type-IIx ?

 

[clearheaded]

just started a thread about this if care to chime in on taking adjuvants during GH use and funny this thread came up as been thinking about this for awhile...

I have interest in immune response as unsure if it was working in a uranium mine or stress OR taking antihistamines to sleep, but started loosing my hair and for a time had alopecia universals ie lost all body hair for a time which is a autoimmune issue. perhaps a perfect storm of all 3..

also speaking of cytokins I think its important people are mindful when taking TB or other thyma peptides that stimulating immune response is not always a good thing for healthy people... scary too many people take it get allergic reactions and are told to keep taking it as "detox" lol... esp in time of covid may not want to have an over reactive immune response. and may be unwise to be taking such peptides with other peptides like GH...

also did immune response have anything to do with why they selected 21Da vs 22Da (could have that backwards)... or was one easier to make or more effective/stronger affinity?

 

[Type-IIx]

I think the main clinical concern with antibodies would be decrease of actual circulating GH, not various noticeable side effects, especially such as those mentioned here. What do you think, @Type-IIx ?

In theory, high levels of anti-GH antibodies could affect GH's effects on growth & metabolism and indeed circlating GH levels, so for example, patients requiring treatment for short stature might see diminished growth velocity. But yes, I agree. And moreover, since modern (r)hGH is so pure and has no clinically significant impact on these antibodies, it's a moot point, or nonconcern.

 

[Type-IIx]

just started a thread about this if care to chime in on taking adjuvants during GH use and funny this thread came up as been thinking about this for awhile...

I have interest in immune response as unsure if it was working in a uranium mine or stress OR taking antihistamines to sleep, but started loosing my hair and for a time had alopecia universals ie lost all body hair for a time which is a autoimmune issue. perhaps a perfect storm of all 3..

also speaking of cytokins I think its important people are mindful when taking TB or other thyma peptides that stimulating immune response is not always a good thing for healthy people... scary too many people take it get allergic reactions and are told to keep taking it as "detox" lol... esp in time of covid may not want to have an over reactive immune response. and may be unwise to be taking such peptides with other peptides like GH...

also did immune response have anything to do with why they selected 21Da vs 22Da (could have that backwards)... or was one easier to make or more effective/stronger affinity?

Sometimes stress can do these things.

I think you are asking about 20 kDa v. 22 kDa GH? The former (20K-GH) may be fairly viewed as a "vestigial" GH isoform, no longer evolutionarily optimized, like the spleen in humans. Compared to 22K-GH, 20K-GH, which comprises 5-10% of circulating GH in blood, lacks 15 amino acid residues, which may reduce its site 1 affinity for the GH-R. Therefore, the torsional force generated by 20K-GH is weaker than that of 22K-GH. This reduces the ability of subunits to rotate when induced by a ligand, which may cause 20K-GH to have a weak signalling ability. 22K-GH is "evolutionarily optimized," in that primate GH can activate non-primate GHR but not vice versa; human GH activates porcine GHR more strongly than porcine, etc.

 

[janoshik]

Sometimes stress can do these things.

I think you are asking about 20 kDa v. 22 kDa GH? The former (20K-GH) may be fairly viewed as a "vestigial" GH isoform, no longer evolutionarily optimized, like the spleen in humans. Compared to 22K-GH, 20K-GH, which comprises 5-10% of circulating GH in blood, lacks 15 amino acid residues, which may reduce its site 1 affinity for the GH-R. Therefore, the torsional force generated by 20K-GH is weaker than that of 22K-GH. This reduces the ability of subunits to rotate when induced by a ligand, which may cause 20K-GH to have a weak signalling ability. 22K-GH is "evolutionarily optimized," in that primate GH can activate non-primate GHR but not vice versa; human GH activates porcine GHR more strongly than porcine, etc.

FIY and mostly unrelated, but there's a myth running around right now I've heard from multiple sources recently, that Chinese GH is actually 20kDa isoform.

Previously it was 192aa GH, now it's 20kDa one...
Each claim as nonsenical as it gets.

 

[Type-IIx]

FIY and mostly unrelated, but there's a myth running around right now I've heard from multiple sources recently, that Chinese GH is actually 20kDa isoform.

Previously it was 192aa GH, now it's 20kDa one...
Each claim as nonsenical as it gets.

Xian, let's dupe these customers of ours, that we would prefer to deliver substandard product to for... REASONS?... by doing something that is more difficult and expensive than just doing what we know works well and....?????...PROFIT!

When I imagine these labs, I'm not thinking some snot-nosed grad. student aiming to make a quick buck from bodybuilders. I'm thinking exponential-industrial scale manufacturing, in a planned city and economy designed for manufacturing, this laboratory manufacturing a massive line of chemical products; just one of several hundreds of other similarly situated manufacturing plants in the same city doing the same thing. These industrial plants, in my mind's eye, would simply never deviate from producing a pure, quality product almost round-the-clock, rhGH being merely one of hundreds of other chemicals being produced for the world market.

 

[janoshik]

From my capitalist perspective making anything else than the product which is already developed, established and produced on a mass scale (191aa 22kDa) and choosing instead to make something more expensive is nothing short of insane

Even 192aa GH is so rare nowadays, that the cost ratio is probably 1:1000.

 

[EnhanceDeezNutz]

A "biologic" is a drug product that is derived from natural sources (e.g., human, animal, micro-organism). For example, (cadaver) pituitary-derived GH, that was used before the advent of the E. coli recombinant DNA (rDNA) manufacturing process to yield rhGH (and before too the 192AA Somatrem, not Somatropin, that was manufactured by an inclusion body technology rather than rDNA process, also associated with GH antibodies). Pituitary-derived GH was associated with Creutzfeldt-Jakob disease outbreaks.

The modern 191AA recombinant human growth hormone (rhGH) produced from an E. coli rDNA process is associated with very low or insignificant antigenicity. From a large sample clinical trial using 3 different products and measuring antigenicity (formation of GH antibodies)
* Group A: 1.4% antigenicity (rhGH [E. coli])
* Group B: 2.8% antigenicity (rhGH [E. coli])
* Group C: 8.5% antigenicity (rhGH [mammalian cell line])

You can see that rhGH as it exists now has a very low prevalence of clinically insignificant GH antibody formation or antigenicity.

It's just a clean process that yields a very pure product.

What an educational response, thank you!

 

[songsofpyramids]

Whole thread was filled with fascinating information. Thank you for sharing.