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彼のことで何かご存知ですか
Do you know anything about him?

I'm not sure what で is doing in this sentence. It's mentioned in this thread but not broken down in detail.

I'm familiar with Xのこと as "about X" but have no idea about the で part. Maybe it has something to do with the keigo? Obviously we need a particle here, and I'd like to use を, but cannot because there is no verb.

If I convert to less formal speech, is there any difference between the following:

彼のことを知っていますか
彼のことで知っていますか
彼について知っていますか

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No, it doesn't have to do with your example sentence being in 敬語 and the verb in 尊敬語. Note the link @broccoli facemask provides in their comment.

【接続】
名詞［辞書形］＋のことで

【意味】
〜について

【例文】
①N１の文法のことで質問があります
②留学のことで相談したいんだけどいい？
③A：春休みに行きたいところはある？
　B：そのことで話があるんだけど…
④お金のことで話さなきゃいけないことがあるの…

You don't see を in there for two reasons:

  1. 彼のことで ＝ 彼のことについて
  2. を is omitted and if put back should mark 何か

彼のことで/について何か(を)ご存知ですか

何か is the content (内容) of the action "to know", and 彼のこと is the scope (範囲). Literally: "What do you know about him?" Here "what" is the direct object of "know", not "about him". See? English works the same way and also allows us to set a range and talk about the specific content with one verb plus some prepositions.

Let's take a quick look at your sentences at the end:

彼のことを知っていますか

This asks directly and specifically if the listener knows "him" (or something about "him" that the asker has in mind). Depending on the context it could either be "Do you know him?" "Do you know about him?" or even "Do you know what happened to him?"

彼のことで知っていますか
彼について知っていますか

These two sentences mean pretty much the same. Standalone and with nothing else, they sound a little strange to me.

何か彼について知っていますか
何か彼のことで知っていますか

sound more natural to me.

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  • Wasn't thinking properly at all when I suggested を: embarrassing. But, would it really go after 何か? I always thought of 何か acting adverbially. I feel another question coming on.
    – user3856370
    May 2, 2022 at 7:49
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    @user3856370 Yes, it can go after 何か, but may not always in natural sentences. I can't put my finger on when the sentence sounds more natural without を than with. But here's an example with it: 製造業にとっての最適な品質は何かをご存知ですか？
    – Eddie Kal
    May 2, 2022 at 7:55
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    を can certainly go after 何か but your example is a bit different. It should be read as ［製造業にとっての最適な品質は何（である）か］をご存じですか. That か forms a content clause. 何か doesn’t mean “something” there.
    – aguijonazo
    May 2, 2022 at 9:33
  • @aguijonazo Ah that's right! Shouldn't have written that comment in haste before bed. Never a good idea. Too bad I can't edit comments after 5 minutes.
    – Eddie Kal
    May 2, 2022 at 15:27

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